前の章|次の章

漢方薬によるVEGFシグナル経路調節を介した抗血管新生作用による乳がん前病変介入の研究進展

  • role： First author第一作者
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

  • Email：3497634670@qq.com
  • Introduction：柏会坤，硕士，从事中医药防治乳腺疾病专业研究，E-mail：3497634670@qq.com
BAI Huikun1,  
  • role： Corresponding author通信作者
  • Affiliation：

    The First Affiliated Hospital of Yunnan University of Chinese Medicine， Kunming 650021，China

  • Email：huangmin237@163.com
  • Introduction：黄敏，硕士，副主任医师，硕士生导师，从事乳腺疾病的中西医结合诊疗研究，E-mail：huangmin237@163.com
HUANG Min2*,  
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

LI Benfa1,  
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

ZHAO Rong1,  
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

LI Zhuoling1,  
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

ZHAO Dongdong1,  
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

YANG Na1,  
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

BI Awei1,  
  • Affiliation：

    The First Clinical Medical School of Yunnan University of Chinese Medicine， Kunming 650500，China

GAN Yun1

サマリー

乳がんの予防と治療は、世界の公衆衛生分野における喫緊の重要課題となっています。がん前病変（PBC）は乳がん発症過程の重要な病理的移行期であり、顕著な臨床的転換リスクを持っています。PBCの進展に効果的に介入することは、乳がん発症の抑制に重要な臨床的意義を有します。病理学的研究により、異常な血管新生はPBCから乳がんへの転化を促進する主要な病理機序であり、血管内皮成長因子（VEGF）は血管新生を促進する中心的な調節分子として、この過程で鍵となる役割を果たしています。PBCの悪性転化過程は、VEGFを介した促血管新生ネットワークの異常活性化と密接に関連しています。現代医学は手術や内分泌療法により一定の効果を上げていますが、侵襲性、耐性、副作用などの臨床的制限が存在します。近年の研究では、VEGFシグナル系がホスファチジルイノシトール3キナーゼ/プロテインキナーゼB（PI3K/Akt）およびミトゲン活性化プロテインキナーゼ（MAPK）経路、さらに低酸素誘導因子-1α（HIF-1α）/VEGF経路およびδ様タンパク質4（DLL4）/ノッチ1（Notch1）受容体など複数のシグナル経路を介して複雑な制御ネットワークを形成し、PBCの血管新生過程において中核的な役割を担っていることが明らかになっています。漢方薬は多成分協調作用、多経路調節、高い安全性を特徴とし、VEGFシグナル経路を標的として病的血管新生を抑制し、PBCの進行を阻止する点で顕著な優位性を示しています。本稿はVEGFシグナル経路調節の視点から漢方薬による血管新生抑制の最新研究進展を体系的に整理し、漢方薬のPBC早期予防・治療における作用機序と価値を探討し、臨床におけるPBC介入戦略の最適化への参考とすることを目的としています。

キーワード

漢方薬;乳がん前病変;血管内皮成長因子（VEGF）;血管新生;研究進展

References

  1. 1.
    SUNG H，FERLAY J，SIEGEL R L，et al.Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA-Cancer J Clin，2021，71（3）：209-249.
  2. 2.
    TAO X，LI T，GANDOMKAR Z，et al.Incidence，mortality，survival，and disease burden of breast cancer in China compared to other developed countries［J］.Asia Pac J Clin Oncol，2023，19（6）：645-654.
  3. 3.
    MO M，WANG Z Z，ZHENG Y，et al.Breast cancer in the world and China in 2022：An analysis on epidemic status［J］.Acad J Nav Med Univ，2025，46（4）：497-503.
  4. 4.
    ZHANG H T，QIU Y B，SU R，et al.Mechanism of Ruyan Neixiao cream in promoting ferroptosis in breast precancerous lesion cells by regulating Nrf2/SLC7A11/GPX4 signaling pathway［J］.Chin J Exp Tradit Med Form，2025，31（7）：98-107.
  5. 5.
    FOLKMAN J.Tumor angiogenesis：Therapeutic implications［J］.N Engl J Med，1971，285（21）：1182-1186.
  6. 6.
    NILAJA B，AKSHITA S，VIKRANT P，et al.Angiogenesis induction in breast cancer：A paracrine paradigm［J］.Cell Biochem Funct，2021，39（7）：860-873.
  7. 7.
    EROLES P，BOSCH A，PEREZ-FIDALGO J A，et al.Molecular biology in breast cancer：Intrinsic subtypes and signaling pathways［J］.Cancer Treat Rev，2012，38（6）：698-707.
  8. 8.
    ENGEL J，WIEDER V，BAUER M，et al.Prognostic and predictive impact of NOTCH1 in early breast cancer［J］.Breast Cancer Res Treat，2025，209（1）：27-38.
  9. 9.
    CHEN M F，YAO C.Research progress of anti-angiogenic treatment of breast cancer with traditional Chinese medicine［J］.J Hebei North University：Nat Sci Edi，2025，41（6）：61-65.
  10. 10.
    RAMADAN S W，ZAHER M D，ALTAIE M A，et al.Potential therapeutic strategies for lung and breast cancers through understanding the anti-angiogenesis resistance mechanisms［J］.Int J Mol Sci，2020，21（2）：565-565.
  11. 11.
    APTE S R，CHEN S D，FERRARA N.VEGF in signaling and disease：Beyond discovery and development［J］.Cell，2019，176（6）：1248-1264.
  12. 12.
    GOEL H L，MERCURIO A M.VEGF targets the tumour cell［J］.Nat Rev Cancer，2013，13（12）：871-882.
  13. 13.
    GU Y，TANG T，QIU M，et al.Clioquinol inhibits angiogenesis by promoting VEGFR2 degradation and synergizes with Akt inhibition to suppress triple-negative breast cancer vascularization［J］.Angiogenesis，2025，28（2）：13.
  14. 14.
    WANG L，ZHAO L，ZHANG L F，et al.Vascular endothelial growth factor promotes cancer stemness of triple-negative breast cancer via MAPK/ERK pathway［J］.J South Med Univ，2021，41（10）：1484-1491.
  15. 15.
    PARK S A，JEONG M S，HA K T，et al.Structure and function of vascular endothelial growth factor and its receptor system［J］.BMB Rep，2018，51（2）：73.
  16. 16.
    LI Y，RUAN Y，SUN Y L，et al.Effects of nobiletin on proliferation，migration，and invasion of rectal cancer cells by regulating RAS/RAF/MEK/ERK signaling pathway［J］.Drug Eval Res，2024，47（11）：2567-2573.
  17. 17.
    MA X Q，ZUO T，MA X D，et al.Exploring the molecular mechanism of Huayu Mingmu recipe-containing serum on the inhibition of high glucose and VEGF-induced angiogenesis in human retinal microvascilar endothelial cells based on VEGFA/VEGFR2-PI3K/Akt signal axis［J］.Tradit Chin Drug Res Clin Pharmacol，2025，36（2）：197-205.
  18. 18.
    TUFAIL M，HU J J，LIANG J，et al.Predictive，preventive，and personalized medicine in breast cancer：Targeting the PI3K pathway［J］.J Transl Med，2024，22（1）：15.
  19. 19.
    GAO A Q.Shikonin inhibits tumor angiogenesis and tumor growth by targeting MAPK and Akt/mTOR signaling pathway［D］.Kunming：Kunming University of Science and Technology，2020.
  20. 20.
    BAI M，XU P，CHENG R，et al.ROS-ATM-CHK2 axis stabilizes HIF-1α and promotes tumor angiogenesis in hypoxic microenvironment［J］.Oncogene，2025，44（21）：1609-1619.
  21. 21.
    GOU X M，SUN H L，ZHANG Z G，et al.Epigenetic modification of redox regulation in breast cancer［J］.Prog Biochem Biophys，2018，45：1224-1231.
  22. 22.
    YANG Y Z，CHEN W.Expression of fructose-1，6-bisphosphatase 1 and hypoxia-inducible factor 1α in breast cancer and its clinical significance［J］.Chin J Health Lab Technol，2021，31（5）：606-609.
  23. 23.
    ZHANG P C，LIU X，LI M M，et al.AT-533，a novel Hsp90 inhibitor，inhibits breast cancer growth and HIF-1α/VEGF/VEGFR-2-mediated angiogenesis in vitro and in vivo［J］.Biochem Pharmacol，2020，172：113771.
  24. 24.
    FENG M，SANTHANAM R K，XING H，et al.Inhibition of γ-secretase/Notch pathway as a potential therapy for reversing cancer drug resistance［J］.Biochem Pharmacol，2024，220：115991.
  25. 25.
    GAO Y，WANG J，ZHAO M，et al.Atractylenolide Ⅲattenuates angiogenesis in gastric precancerous lesions through the downregulation of delta-like ligand 4［J］.Front Pharmacol，2022，13：797805.
  26. 26.
    SHI Q，XUE C，ZENG Y，et al.Notch signaling pathway in cancer：From mechanistic insights to targeted therapies［J］.Signal Transduct Target Ther，2024，9（1）：128.
  27. 27.
    ZHANG X L，XU G Y，WANG S Z，et al.Effects of miR-186-5p on vascular endothelial cell injury and FGF2/FGFR1 signaling pathway in rat model of coronary heart disease［J］.Tianjin Med J，2021，49（11）：1169-1174.
  28. 28.
    LIN J C，CHEN X D，JIANG Q.Role of phosphorylated Tyr951 signal protein in endothelial cell migration in diabetic rats［J］.Strait Pharm J，2019，31（8）：28-30.
  29. 29.
    MATSUMOTO T，BOHMAN S，DIXELIUS J，et al.VEGF receptor‐2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis［J］.EMBO J，2005，24（13）：2342-2353.
  30. 30.
    WEI Q S，LIANG J，QI M H，et al.Research progress on the mechanism of acupuncture and moxibustion promoting angiogenesis［J］.J Emerg Syndromes Tradi Chin Med，2021，30（2）：369-372.
  31. 31.
    ZHONG J，SU M，JIANG Y，et al.VEGFR2 targeted microbubble-based ultrasound molecular imaging improving the diagnostic sensitivity of microinvasive cervical cancer［J］.J Nanobiotechnology，2023，21（1）：220.
  32. 32.
    LONG J Y，LIU H.Effect of Chaishao Rupi granules on the expression of MVD and VEGF protein in rats with mammary atypical hyperplasia［J］.Guid J Tradi Chin Med Pharm，2024，30（10）：32-35，47.
  33. 33.
    LIU Y，SONG L，LIN M.Correlation between the expression of VEGF-C，HIF-1α and angiogenesis in breast cancer tissues［J］.Chin Fore Med Res，2024，22（28）：73-77.
  34. 34.
    DENG J L，GONG Y F，WANG X P，et al.Effect of Sanjie Xiaofang on angiogenesis in tumor-bearing nude mice with thyroid follicular carcinoma by regulating HIF-1α/VEGF signaling pathway［J］.Chin Tradit Pat Med，2024，46（11）：3795-3799.
  35. 35.
    SONG X，XIAO J，WU J，et al.Decellularized amniotic membrane promotes the anti-inflammatory response of macrophages via PI3K/Akt/HIF-1α pathway［J］.Chin Chem Lett，2025，36（1）：109844.
  36. 36.
    YAO Y F，GAO F，ZHANG X S，et al.The anti-angiogenesis effect of interventional embolization using drug-loaded microspheres with bevacizumab in treating rabbit VX2 hepatocellular carcinoma［J］.J Interwent Radio，2021，30（3）：254-257.
  37. 37.
    ZHONG N，ZHUANG W，HUANG Q，et al.Apatinib inhibits the growth of small cell lung cancer via a mechanism mediated by VEGF，PI3K/Akt and Ki‐67/CD31［J］.J Cell Mol Med，2021，25（21）：10039-10048.
  38. 38.
    PENG S，ZHANG Y，PENG H，et al.Intracellular autocrine VEGF signaling promotes EBDC cell proliferation，which can be inhibited by Apatinib［J］.Cancer Lett，2016，373（2）：193-202.
  39. 39.
    ZENG Y F，ZHAO D，WANG J Y，et al.Progress of Chinese medicine in regulating related signalling pathways to prevent and control breast cancer and precancerous lesions［J］.Chin J Exp Tradit Med Form，2026，32（5）：290-301.
  40. 40.
    CHENG X L.Meta-analysis on the intervention of traditional Chinese medicine in the breast cancer precancerous lesions and the expression of EMT markers in benign and malignant breast tissues［D］.Jinan：Shandong University of Traditional Chinese Medicine，2020.
  41. 41.
    MENG B B，RUI R，YIN N N，et al.Meta-analysis of TCM in treating breast cancer precancerous lesions［J］.Acta Chin Med，2020，35（2）：433-440.
  42. 42.
    YANG H，LONG J Y，GONG J，et al.Effects of Rutong Ruanjian tablets on angiogenesis in a rat model of preneoplastic breast cancer of Liver-Qi stagnation and blood stasis pattern via DLL4/Notch1/Hes1 pathway［J］.Chin Tradit Pat Med，2025，47（3）：774-781.
  43. 43.
    LONG J Y.Experimental investigation on the effect of Chaishao RuPi pellet on the expressions of MVD and VEGF proteins in breast precancerous lesion of rats［D］.Changsha：Hunan University of Chinese Medicine，2021.
  44. 44.
    ZHANG Y J，HUANG P W，ZHANG Y T，et al.Effect and mechanism of Xihuang pill on rats with precancerous lesions of breast［J］.China J Chin Mater Med，2023，48（13）：3546-3555.
  45. 45.
    GUAN Y，GUAN X.Clinical observation on Xihuang capsule in the treatment of precancerous lesions of breast cancer［J］.Chin Med Mod Dis Educ China，2023，21（8）：63-65.
  46. 46.
    LI D H，FAN H F，SUN C X，et al.Effects of liquid extract of Xihuang pill on mTOR and VEGF expression in precancerous cells of human breast cancer［J］.Hunan J Tradit Chin Med，2017，33（6）：145-148.
  47. 47.
    LIN S，JIANG X，ZHANG G，et al.The Chinese herbal formula Ruyan Neixiao cream inhibits angiogenesis of precancerous breast lesions via regulation of Ras/Raf/MEK/ERK signaling pathway［J］.Integr Cancer Ther，2022，doi：.
  48. 48.
    LIANG S J，ZHANG G J，MA M，et al.Effect of topical Ruyan Neixiao cream for VEGF and FGF2 expression in rat breast with mammary precancerous lesions［J］.J Jinan Univ Nat Sci Med Ed，2015，36（6）：484-489.
  49. 49.
    DENG W F，PEI X H.The influence of capsule for dispersing breast mass on the expression of CXCR4 and VEGF in breast tissue of rats with precancerous lesion of breast cancer［J］.Henan Tradit Chin Med，2020，40（9）：1360-1364.
  50. 50.
    DONG X.Study on the mechanism of Zaoqiao Xiaopi granule on the precancerous lesion of breast cancer SD rats with liver stagnation and phlegm coagulation［D］.Xi'an：Shanxi University of Chinese Medicine，2020.
  51. 51.
    LI Z H.Mechanism of Chinese medicine Jiawei Fengfang pill on prevention and treatment of breast cancer［D］.Hohhot：Inner Mongolia Medical University，2020.
  52. 52.
    DENG W F，JIA Y，PEI X H.Effects of Xiaoyao pills on the expression of CXCR4 and VEGF in breast tissue of rats with breast carcinoma precancerous lesion［J］.China J Tradit Chin Med Pharm，2019，34（4）：1386-1390.
  53. 53.
    TANG L L.Effect of Xiaohe granule on the expression of FLK-1 and FGF-2 in precancerous breast lesion of rats［D］.Hefei：Anhui University of Chinese Medicine，2017.
  54. 54.
    SHANG G B，ZENG L P，ZHAO Y，et al.Effect of Erzhi pill on expressions of VEGF and MMP-9 in induced rat breast cancer［J］.Chin J Exp Tradit Med Form，2013，19（13）：270-273.
  55. 55.
    WANG C，XU Y L，YAO C.Mechanism of chronic oxidative stress on Danlu capsules regulating PI3K-Akt pathway to improve breast cancer precancerous lesions［J］.China J Tradit Chin Med Pharm，2024，39（11）：6049-6053.
  56. 56.
    WANG Y L，CHEN F，WANG F.Effect and mechanism of Yanghe Huayan decoction on breast precancerous lesions［J］.Chin Arch Tradit Chin Med，2021，39（3）：44-47.
  57. 57.
    WU X X.The clinical and experimental research of VEGF-C and VEGFR-3 through Yanghe Huayan decoction's effect on breast precancerous lesion［D］.Jinan：Shandong University of Traditional Chinese Medicine，2014.
  58. 58.
    LI F F，LIU X F，ZHANG Y，et al.Effect of Shugan Jianpi decoction on lymphangiogenesis in nude mice with precancerous lesions of breast cancer［J］.Mod J Integr Tradit Chin West Med，2019，28（21）：2292-2296.
  59. 59.
    LI L P，YANG X，WANG R R，et al.Effects of Shugan Jianpi Jiedu formula on angiogenesis of breast tissue in breast cancer rat model with precancerous lesion of liver Qi stagnation syndrome［J］.J Hunan Univ Chin Med，2019，39（10）：1195-1199.
  60. 60.
    LI L P，SHI J，HE D，et al.Preventive and therapeutic mechanism of Shugan Jianpi Jiedu decoction on precancerous lesions of breast cancer［J］.Chin J Mod Appl Pharm，2024，41（5）：619-625.
  61. 61.
    LI L P，SHI J，TAN X N，et al.Shugan Jianpi Jiedu formula inhibits gonadal axis and PI3K/Akt/mTOR signaling pathways to affect breast precancerous lesions［J］.Chin J Integr Tradit Chin West Med，2024，44（8）：959-965.
  62. 62.
    LI L P.Exploration on the molecular mechanism of Shugan Jianpi Jiedu decoction in the prevention and treatment of breast precancerous lesions based on ER and PI3K/Akt/mTOR pathway［D］.Changsha：Hunan University of Chinese Medicine，2022.
  63. 63.
    ZHAO J，PANG T，JIAO J，et al.Xiaotan Jieyu prescription alleviates breast precancerous lesions through PI3K/Akt signaling pathway［J］.Evid Based Complement Alternat Med，2020，doi：.
  64. 64.
    ZHAO J，WEI P K，XIU L J，et al.Effect of Xiaotan Jieyu decoction on PI3K/Akt pathway of MCF-10AT cells and its mechanism［J］.Acad J Second Mil Med Univ，2017，38（4）：520-523.
  65. 65.
    LIU Y，ZHANG G，MA Y，et al.Eugenol inhibits NEAT1 as a ceRNA in pre-cancerous breast lesions［J］.Heliyon，2025，11（1）：e41353.
  66. 66.
    YANG L X，DENG W F，CHEN H，et al.Effect of diterpenoids on breast cancer precancerous lesions，liver depression and kidney deficiency pattern model rats［J］.Chin J Exp Tradit Med Form，2018，24（2）：140-145.
  67. 67.
    SONG A L，XU Z G.Zedoary turmeric oil effect on rats with precancerous lesions of breast carcinoma in VEGF mRNA expression［J］.China Arch Tradit Chin Med，2012，30（4）：679-681.
  68. 68.
    XU Z G，SONG A L，YIN Y K，et al.Effect of zedoray turmeric oil for VEGF mRNA expression in precancerous lesion of rats mammary［J］.Chin J Cancer Prev Treat，2012，19（8）：570-574.
  69. 69.
    XU Z G.Study about zedoray turmeric oil on angiogenesis and expression of related regulatory factors in breast precancerous of rats［D］.Jinan：Shandong University of Traditional Chinese Medicine，2012.

続きを読む

The above content is generated by Large Model Translation. The translated content is for reference only. We do not assume any commercial or legal responsibilty for any consequences arising from the use of our website