As an autophagy inhibitor, Chloroquine (CQ) showed anti-tumor effect on several types of cancer and paclitaxel (PTX) is widely used in the treatment of esophageal carcinoma patients, but chemoresistance remains a major hurdle for PTX application due to the cytoprotective autophagy. Therefore, the aim of this study was to investigate whether CQ could elevate the anti-tumor effect of PTX on esophageal carcinoma cell line EC109 and explore the potential molecular mechanisms. We confirmed the suppressive effect of PTX on EC109 by MTT, scratch test, transwell and soft agar assay. And we detected the key proteins in Akt/mTOR pathway, as well as the autophagy marker LC3 and p62 through Western Blot. In addition, GFP-LC3 plasmid was transfected into EC109 cells to monitor the autophagosome after CQ and PTX treatment. Ultimately, we observed the alterations in the proliferation and colony formation abilities of EC109 after knocking down mTOR by shRNA. We confirmed PTX could suppress the proliferation, migration and colony formation abilities of EC109, and CQ could sensitize the inhibition effect of PTX by inhibiting autophagy through Akt/mTOR pathway. Furthermore, inhibiting Akt/mTOR pathway initiated autophagy and enhanced the sensitivity of EC109 to CQ and PTX. In summary, we suggest CQ could be used as a potential chemosensitizer for PTX in esophageal carcinoma treatment.

中文翻译：

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氯喹通过抑制自噬使食管癌 EC109 细胞对紫杉醇敏感

作为一种自噬抑制剂，氯喹（CQ）对多种癌症具有抗肿瘤作用，紫杉醇（PTX）广泛用于食管癌患者的治疗，但由于细胞保护性自噬，化疗耐药仍然是其应用的主要障碍。因此，本研究的目的是探讨CQ是否可以增强PTX对食管癌细胞系EC109的抗肿瘤作用，并探讨其潜在的分子机制。我们通过MTT、划痕试验、Transwell和软琼脂实验证实了PTX对EC109的抑制作用。我们通过Western Blot检测了Akt/mTOR通路中的关键蛋白，以及自噬标志物LC3和p62。此外，将GFP-LC3质粒转染至EC109细胞中以监测CQ和PTX处理后的自噬体。最终，我们观察到shRNA敲除mTOR后EC109增殖和集落形成能力的变化。我们证实PTX可以抑制EC109的增殖、迁移和集落形成能力，而CQ可以通过Akt/mTOR通路抑制自噬来敏化PTX的抑制作用。此外，抑制 Akt/mTOR 通路启动自噬并增强 EC109 对 CQ 和 PTX 的敏感性。总之，我们建议 CQ 可作为 PTX 治疗食管癌的潜在化疗增敏剂。