ATG 4B Serves a Crucial Role in RCE-4-Induced Inhibition of the Bcl-2-Beclin 1 Complex in Cervical Cancer Ca Ski Cells.
ATG 4B Serves a Crucial Role in RCE-4-Induced Inhibition of the Bcl-2-Beclin 1 Complex in Cervical Cancer Ca Ski Cells.
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ATG 4B 在 RCE-4 诱导的宫颈癌 Ca Ski 细胞中 Bcl-2-Beclin 1 复合物抑制中发挥关键作用
DOI：
10.3390/ijms222212302
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发表时间：
2021-11-14
影响因子：
5.6
通讯作者：
Chen JF
中科院分区：
文献类型：
--
作者：
You FF;Zhang J;Cheng F;Zou K;Zhang XQ;Chen JF
RCE-4是一种从吉祥草中分离的甾体皂苷，以前已经研究过，并通过诱导Ca Ski细胞的程序性细胞死亡（PCD）表现出有希望的抗宫颈癌特性。考虑到癌细胞发展了多种途径来逃避化疗诱导的PCD，因此，迫切需要进一步探索其作用的潜在机制。本研究以细胞凋亡的关键调控因子Bcl-2-Beclin 1复合物为靶点，深入阐明RCE-4抗宫颈癌的分子机制。用免疫共沉淀法检测RCE-4对Bcl-2-Beclin 1复合物的影响。此外，自噬相关基因（ATG）由于其在PCD中的特殊作用也被分析。结果表明，RCE-4通过多种途径抑制Ca Ski细胞中Bcl-2-Beclin 1复合物的形成，而ATG 4 B蛋白在此过程中起关键辅助因子的作用。此外，基于上述，通过应用ATG 4 B siRNA质粒抑制ATG 4 B的表达，RCE-4对Ca Ski细胞的敏感性显著增强。
RCE-4, a steroidal saponin isolated from Reineckia carnea, has been studied previously and has exhibited promising anti-cervical cancer properties by inducing programmed cell death (PCD) of Ca Ski cells. Considering the cancer cells developed various pathways to evade chemotherapy-induced PCD, there is, therefore, an urgent need to further explore the potential mechanisms underlying its actions. The present study focused on targeting the Bcl-2–Beclin 1 complex, which is known as the key regulator of PCD, to deeply elucidate the molecular mechanism of RCE-4 against cervical cancer. The effects of RCE-4 on the Bcl-2–Beclin 1 complex were investigated by using the co-immunoprecipitation assay. In addition, autophagy-related genes (ATG) were also analyzed due to their special roles in PCD. The results demonstrated that RCE-4 inhibited the formation of the Bcl-2–Beclin 1 complex in Ca Ski cells via various pathways, and ATG 4B proteins involved in this process served as a key co-factor. Furthermore, based on the above, the sensitivity of RCE-4 to Ca Ski cells was significantly enhanced by inhibiting the expression of the ATG 4B by applying the ATG 4B siRNA plasmid.
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