Mechanism of Bicalutamide to Breast Cancer Cell Lines MDA-MB-453 and Inhibitory Effects of Its Combination with Everolimus
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摘要:目的
探讨比卡鲁胺对雄激素受体（AR）阳性乳腺癌细胞侵袭迁移能力的影响及相关作用机制，以及mTOR抑制剂依维莫司联合比卡鲁胺对MDA-MB-453细胞株增殖作用的影响。
方法Western blot方法检测比卡鲁胺作用前后乳腺癌细胞株mTOR、p-mTOR和p-S6表达的变化，Transwell迁移侵袭实验检测比卡鲁胺处理前后细胞活性的变化，MTT法检测依维莫司联合比卡鲁胺对MDA-MB-453乳腺癌细胞株增殖作用的影响，通过金正均法计算Q值，评估两药联用对乳腺癌细胞株MDA-MB-453抑制作用的效果。
结果比卡鲁胺作用6天后，MDA-MB-453细胞中mTOR、p-mTOR和p-S6的表达明显降低（Ρ =0.034, 0.05, 0.03），MDA-MB-453细胞的迁移侵袭能力较用药前受到明显抑制（迁移：t =4.88, Ρ =0.001；侵袭：t =2.684, Ρ =0.028）。比卡鲁胺联合依维莫司作用后，MDA-MB-453细胞株增殖受到抑制，各浓度下Q值均大于1.15。
结论比卡鲁胺能抑制MDA-MB-453乳腺癌细胞株的侵袭迁移，其抑制效果受AR的表达量影响。比卡鲁胺联合依维莫司可以协同抑制AR阳性乳腺癌细胞的增殖。
Abstract:ObjectiveTo investigate the effect of bicalutamide on migration and invasion of androgen receptor(AR) positive breast cancer cells and related mechanism, and the effect of mTOR inhibitor everolimus combined with bicalutamide on the proliferation of MDA-MB-453 cells.
MethodsWestern blot was used to detect the expression change of mTOR, p-mTOR and p-S6 in breast cancer cell lines before and after bicalutamide treatment. Transwell assay was used to detect the cell viability. MTT assay was used to detect the proliferation of MDA-MB-453 cells treated by the combination of bicalutamide and everolimus. The combined effect of the two drugs was calculated by Jin Zhengjun's method.
ResultsAfter six days of bicalutamide treatment, the expression of mTOR, p-mTOR and p-S6 were decreased in MDA-MB-453 cells (Ρ =0.034, 0.05, 0.03). The invasion and migration were inhibited in MDA-MB-453 cells (migration: t =4.88, P =0.001, invasion: t =2.684, P =0.028). The proliferation of MDA-MB-453 cells was inhibited after the treatment of bicalutamide combined with everolimus, and the Q value were all greater than 1.15.
ConclusionBicalutamide could inhibit the invasion and migration of MDA-MB-453, and the inhibition effect is affected by the expression level of AR. The combination of bicalutamide and everolimus could synergistically inhibit the proliferation of AR positive breast cancer cells.
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Key words:
- Bicalutamide /
- Everolimus /
- Breast cancer /
- Drug combination
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Competing interests: The authors declare that they have no competing interests.作者贡献张玉琴：实验实施，撰写论文陆云飞：指导实验，数据整理张海添：指导课题，设计实验
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图 1 比卡鲁胺作用前后MDA-MB-231、MCF-7和MDA-MB-453细胞中mTOR、p-mTOR和p-S6表达
Figure 1 Expression of mTOR, p-mTOR and p-S6 in breast cancer cell lines MDA-MB-231, MCF-7 and MDA-MB-453 before and after bicalutamide treatment
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图 2 三株乳腺癌细胞株迁移(A)和侵袭(B)实验结果
Figure 2 Migration (A) and invasion (B) tests of three breast cancer cell lines
表 1 不同浓度依维莫司与比卡鲁胺联合作用于MDA-MB-453细胞的抑制率(%)
Table 1 Inhibition rates of different concentration of everolimus combined with bicalutamide on MDA-MB-453 cells (%)
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