蘆薈大黃素對於人類乳癌的作用及其機轉之研究

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蘆薈大黃素對於人類乳癌的作用及其機轉之研究

The Effects and Underlying Mechanisms of Aloe-Emodin on Human Breast Cancer

曾信順 , Ph.D　　Advisor：廖雅芳;曾耀銘　　

繁體中文

蘆薈大黃素；乳癌；抗賀爾蒙療法；細胞凋亡； Aloe-emodin ； Human breast cancer ； Anti-hormonal therapy ； Apoptosis

Abstract │ Reference (35) │ Altmetrics

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Aloe-emodin (AE) derived from aloe vera and rhubarb, is a nature anthraquinone and exhibits anti-cancer activities via multiple regulatory mechanisms in various cancers. MCF-7 cancer cell was used in this study to analyze the effects and underlying mechanisms of Aloe-Emodin on human breast cancer. MCF-7 cell line belongs to hormone receptor positive human breast cancer. Tamoxifen, an anti-hormonal drug, plays an important role in the treatment of hormone-positive human breast cancer. Therefore, AE and Tamoxifen were used to explore the possible therapeutic effects of breast cancer and potential mechanisms in this study. We found that tamoxifen had synergistic effect with AE in MCF-7 cells. After combined with tamoxifen and AE, the survival rate of MCF-7 cells was reduced significantly. Besides, AE increased reactive oxygen species (ROS) and decreased the mitochondrial membrane potential and may contribute to the apoptosis of MCF-7 cells treated with tamoxifen. AE combined with tamoxifen in MCF-7 cells regulated the expression of Bcl-xl, Bim, Bax, cleavaged of Caspase 7 and poly ADP-ribose polymerase (PARP). It was shown that AE combined with tamoxifen could enhance apoptosis through the intrinsic pathway. Furthermore, AE promoted tamoxifen-inhibited the activation of ERα protein and the growth of ERα-positive breast cancer cells. After AE combined tamoxifen treatment, Ras protein, ERK1/2 protein, and phosphorylated ERK, PI3K and mTOR proteins were decreased in MCF-7 cells. Therefore, AE had a anti-cancer activity via PI3K/mTOR pathway. In conclusion, AE enhanced the therapeutic effect of tamoxifen on estrogen receptor-positive breast cancer cells via two pathways: the first was the reduction of cancer cells proliferation via the estrogen receptor pathway. The second was the induction of cell apoptosis. Under the basis of this study, we had finished the importance of AE in the chemosensitivity induced by tamoxifen to increase the chances of cancer resistance in cancer patients.

Reference ( 35 ) 〈TOP〉

Cha, T. L., Qiu, L., Chen, C. T., Wen, Y. and Hung, M. C., "Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth," Cancer Research, Vol. 65, No. 6, pp.2287-2295 (2005).
連結：
Chang, Y. C., Lai, T. Y., Yu, C. S., Chen, H. Y., Yang, J. S., Chueh, F. S., Lu, C. C., Chiang, J. H., Huang, W. W., Ma, C. Y. and Chung, J. G., "Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo," Evidence-based complementary and alternative medicine Vol. 2011, No. pp.523596 (2011).
連結：
Chihara, T., Shimpo, K., Beppu, H., Yamamoto, N., Kaneko, T., Wakamatsu, K. and Sonoda, S., "Effects of Aloe-emodin and Emodin on Proliferation of the MKN45 Human Gastric Cancer Cell Line," Asian Pacific journal of cancer prevention, Vol. 16, No. 9, pp.3887-3891 (2015).
連結：
Chiu, T. H., Lai, W. W., Hsia, T. C., Yang, J. S., Lai, T. Y., Wu, P. P., Ma, C. Y., Yeh, C. C., Ho, C. C., Lu, H. F., Wood, W. G. and Chung, J. G., "Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells," Anticancer research, Vol. 29, No. 11, pp.4503-4511 (2009).
連結：
Eisenhauer, E. A., ten Bokkel Huinink, W. W., Swenerton, K. D., Gianni, L., Myles, J., van der Burg, M. E., Kerr, I., Vermorken, J. B., Buser, K., Colombo, N. and et al., "European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion," Journal of clinical oncology, Vol. 12, No. 12, pp.2654-2666 (1994).
連結：

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