Department of Oncology, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui 241002, P.R. China.
Anhui Province Key Laboratory of Active Biological Macromolecules, Wannan Medical College, Wuhu, Anhui 241002, P.R. China.
Int J Mol Med. 2018 Oct;42(4):2089-2097. doi: 10.3892/ijmm.2018.3789. Epub 2018 Jul 19.
Inducible heat shock protein 70 (HSP70; also known as HSPA1 or HSP72) is implicated in cancer. As a stress‑inducible heat shock protein, HSP70 is highly expressed in a variety of cancers and correlates with metastasis, chemotherapy resistance and tumor prognosis. The present study demonstrated that suppression of HSP70 through the specific inhibitor pifithrin‑µ or by HSP70 knockdown enhanced cisplatin‑induced apoptosis in HGC‑27 gastric cancer cells. By contrast, upregulation of HSP70 through transfection of a HSP70 overexpressing plasmid decreased cisplatin‑induced HGC‑27 cell apoptosis. In exploring the underlying molecular mechanisms, the present results revealed that HSP70 antagonized cisplatin‑induced HGC‑27 cell apoptosis by regulating the mitogen‑activated protein kinase (MAPK) signaling pathway. In addition, suppressing the MAPK pathway enhanced cisplatin‑induced HGC‑27 cell apoptosis. Collectively, the present findings suggest that inhibition of HSP70 expression enhanced the sensitivity of HGC‑27 cells to cisplatin via the MAPK signaling pathway, and that HSP70 may serve as a potential therapeutic target in gastric cancer.
诱导型热休克蛋白 70（HSP70；也称为 HSPA1 或 HSP72）与癌症有关。作为一种应激诱导的热休克蛋白，HSP70 在多种癌症中高度表达，并与转移、化疗耐药和肿瘤预后相关。本研究表明，通过特异性抑制剂 pifithrin-µ 或 HSP70 敲低抑制 HSP70，可增强顺铂诱导的 HGC-27 胃癌细胞凋亡。相反，通过 HSP70 过表达质粒转染上调 HSP70，可降低顺铂诱导的 HGC-27 细胞凋亡。在探索潜在的分子机制时，本研究结果表明，HSP70 通过调节丝裂原活化蛋白激酶（MAPK）信号通路拮抗顺铂诱导的 HGC-27 细胞凋亡。此外，抑制 MAPK 通路可增强顺铂诱导的 HGC-27 细胞凋亡。综上所述，本研究结果表明，抑制 HSP70 表达通过 MAPK 信号通路增强了 HGC-27 细胞对顺铂的敏感性，HSP70 可能成为胃癌的潜在治疗靶点。
