Background:

Tamoxifen is one of the medicines for adjuvant endocrine therapy of hormone-dependent breast cancer. However, development of resistance to tamoxifen occurs inevitably during treatment. This study aimed to determine whether sensitivity of tamoxifen-resistant breast cancer cells (TAM-R) could be reinstated by tetrandrine (Tet).

Methods:

All experiments were conducted in TAM-R cells derived from the MCF-7 breast cancer cell line by long-term tamoxifen exposure. Cell growth, apoptosis, and autophagy were end-points that evaluated the effect of Tet (0.9 μg/ml, 1.8 μg/ml, and 3.75 μg/ml) alone or in combination with TAM (1 μM). Cell apoptosis was determined by an ELISA assay and autophagy was determined by fluorescent staining using the Enzo autophagy detection kit. Immunoblotting was used to evaluate markers for apoptosis, autophagy, and related signal pathway molecules.

Results:

Growth of TAM-R cells was significantly inhibited by Tet. Combination of Tet with tamoxifen induced a greater inhibition on cell growth than tamoxifen alone, which was predominantly due to enhancement of pro-apoptotic effect of TAM by Tet. Autophagy was significantly inhibited in TAM-R cells treated with Tet plus TAM as shown by increased autophagosomes and the levels of LC3-II and p62. At 0.9 μg/ml, Tet increased the levels of both apoptosis and autophagy markers. Among them increase in p53 levels was more dramatic.

Conclusions:

Tet as a monotherapy inhibits TAM-R cells. Tet potentiates the pro-apoptotic effect of TAM via inhibition of autophagy.

中文翻译：

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用粉防己碱恢复耐他莫昔芬的乳腺癌细胞对他莫昔芬的敏感性

背景：

他莫昔芬是激素依赖性乳腺癌辅助内分泌治疗的药物之一。然而，在治疗过程中不可避免地会出现对他莫昔芬的耐药性。本研究旨在确定粉防己碱 (Tet) 是否可以恢复对他莫昔芬耐药的乳腺癌细胞 (TAM-R) 的敏感性。

方法：

所有实验均在源自 MCF-7 乳腺癌细胞系的 TAM-R 细胞中进行，该细胞通过长期暴露于他莫昔芬。细胞生长、细胞凋亡和自噬是评估 Tet（0.9 μg/ml、1.8 μg/ml 和 3.75 μg/ml）单独或与 TAM（1 μM）组合作用的终点。通过ELISA测定确定细胞凋亡，并使用Enzo自噬检测试剂盒通过荧光染色确定自噬。免疫印迹用于评估细胞凋亡、自噬和相关信号通路分子的标志物。

结果：

Tet 显着抑制了 TAM-R 细胞的生长。Tet 与他莫昔芬的组合比单独的他莫昔芬对细胞生长的抑制作用更大，这主要是由于 Tet 增强了 TAM 的促凋亡作用。如自噬体增加以及 LC3-II 和 p62 水平所示，在用 Tet 加 TAM 处理的 TAM-R 细胞中，自噬受到显着抑制。在 0.9 μg/ml 时，Tet 增加了细胞凋亡和自噬标志物的水平。其中 p53 水平的增加更为显着。

结论：

Tet 作为单一疗法抑制 TAM-R 细胞。Tet 通过抑制自噬增强 TAM 的促凋亡作用。