Background

Mitochondrial unfolded protein response plays an important role in the occurrence and development of breast cancer. However, the role of mitochondrial unfolded protein response (UPR^mt) in the sensitivity of breast cancer to cisplatin chemotherapy has not yet been cleared.

Objectives

The purpose of this study is to explore the role of mitochondrial unfolded protein response in breast cancer sensitivity to cisplatin.

Methods

In this study, qRT-PCR, Western blotting, Immunofluorescence, CCK-8, Colony formation, Transwell assay and TUNEL staining assay were used to confirm the role of UPR^mt in breast cancer cells treated with cisplatin.

Results

Cisplatin increased the levels of UPR^mt including CLPP, HSP60, LONP1 in MCF7 and MDA-MB-231 cells. UPR^mt inducer Nicotinamide ribose (NR) could promote the proliferation and invasion of breast cancer cells treated with cisplatin. Importantly, SIRT3 was discovered to increase UPR^mt in breast cancer cells and silencing of SIRT3 could inhibit the effect of NR in breast cancer.

Conclusions

UPR^mt regulated by SIRT3 could protect breast cancer cell from cisplatin. Controlling SIRT3-induced UPR may be a potential therapeutic target to increase the sensitivity of breast cancer chemotherapy.

中文翻译：

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SIRT3介导的线粒体未折叠蛋白反应削弱了乳腺癌对顺铂的敏感性

背景

线粒体未折叠蛋白反应在乳腺癌的发生发展中发挥着重要作用。然而，线粒体未折叠蛋白反应（UPR ^mt）在乳腺癌对顺铂化疗敏感性中的作用尚未明确。

目标

本研究的目的是探讨线粒体未折叠蛋白反应在乳腺癌对顺铂敏感性中的作用。

方法

在这项研究中，qRT-PCR、蛋白质印迹、免疫荧光、CCK-8、集落形成、Transwell 测定和 TUNEL 染色测定用于确认 UPR ^mt在顺铂处理的乳腺癌细胞中的作用。

结果

顺铂增加了 UPR ^mt的水平，包括 MCF7 和 MDA-MB-231 细胞中的 CLPP、HSP60、LONP1。UPR ^mt诱导剂烟酰胺核糖（NR）可以促进顺铂处理的乳腺癌细胞的增殖和侵袭。重要的是，发现 SIRT3 可以增加乳腺癌细胞中的 UPR ^mt，而沉默 SIRT3 可以抑制 NR 在乳腺癌中的作用。

结论

SIRT3调控的UPR ^mt可以保护乳腺癌细胞免受顺铂的侵害。控制 SIRT3 诱导的 UPR 可能是增加乳腺癌化疗敏感性的潜在治疗靶点。