Autophagy is a catabolic process for cells that can provide energy sources and allows cancer cells to evade cell death. Therefore, studies on the combination of autophagy inhibitors with drugs are increasing as a new treatment modality in cancer. Previously, we reported the anti-tumor activity of a Palladium (Pd)(II) complex against different types of cancer in vitro and in vivo. Chloroquine (CQ), the worldwide used anti-malarial drug, has recently been focused as a chemosensitizer in cancer treatment. The aim of this study was to investigate the efficacy of a combined treatment of these agents that work through different mechanisms to provide an effective treatment modality for metastatic prostate cancer that is certainly fatal. Metastatic prostate cancer cell lines (PC-3 and LNCaP) were treated with Pd (II) complex, CQ, and their combination. The combination enhanced apoptosis by increasing phosphatidylserine translocation and pro-apoptotic proteins. Apoptosis was confirmed by the use of apoptosis inhibitor. The formation of acidic vesicular organelles (AVOs) was observed by acridine orange staining in fluorescence microscopy. The Pd (II) complex increased AVOs formation in prostate cancer cells and CQ-pretreatment has potentiated this effect. Importantly, treatment with CQ suppressed the pro-survival function of autophagy, which might have contributed to enhanced cytotoxicity. In addition, PI3K/AKT/mTOR-related protein expressions were altered after the combination of treatments. Our results suggest that combination treatment enhances apoptotic cell death possibly via the inhibition of autophagy, and may therefore be regarded as a novel and better approach for the treatment of metastatic prostate cancer.

自噬是细胞的分解代谢过程，可以提供能量来源，并使癌细胞逃避细胞死亡。因此，自噬抑制剂与药物组合的研究作为癌症的一种新治疗方法正在增加。以前，我们报道了钯（Pd）（II）配合物在体外对不同类型癌症的抗肿瘤活性和体内。全世界使用的抗疟疾药物氯喹（CQ）最近在癌症治疗中被用作化学增敏剂。这项研究的目的是研究这些药物的联合治疗的功效，这些药物通过不同的机制为转移性前列腺癌提供有效的治疗方法，这种方法肯定是致命的。用Pd（II）复合物，CQ及其组合处理转移性前列腺癌细胞系（PC-3和LNCaP）。该组合通过增加磷脂酰丝氨酸易位和促凋亡蛋白来增强细胞凋亡。通过使用凋亡抑制剂来确认凋亡。在荧光显微镜下通过in啶橙染色观察到酸性水泡细胞器（AVOs）的形成。Pd（II）复合物增加了前列腺癌细胞中AVO的形成，CQ预处理增强了这种作用。重要的是，CQ治疗抑制了自噬的促生存功能，这可能有助于增强细胞毒性。另外，在组合治疗后，PI3K / AKT / mTOR相关蛋白的表达也发生了改变。我们的结果表明，联合治疗可能会增加凋亡细胞的死亡通过抑制自噬，因此可以被认为是治疗转移性前列腺癌的一种新颖且更好的方法。