Chloroquine diphosphate

Chloroquine diphosphate（氯喹宁二磷酸盐）被用作抗疟疾药物，也可通过诱导自噬，从而增加肿瘤细胞对放疗和化疗的敏感性 [1]。

据报道，chloroquine diphosphate可诱导自噬，因而可作为放疗和化疗的佐剂，用于抵抗癌细胞的增殖或转移 [2]。Chloroquine diphosphate诱导细胞自噬的机制是诱导G1期停滞，上调p27和p53的表达，而下调CDK2和细胞周期蛋白D1的表达 [3]。

除了抗疟疾，chloroquine diphosphate对细胞凋亡也起作用。CNE-2人鼻咽癌细胞用chloroquine diphosphate预处理后通过增加细胞自噬的比例，增强电离辐射诱导的细胞凋亡 [4]。在人结肠癌DLD-1细胞中，5-FU与chloroquine diphosphate联合治疗通过诱导自噬，抑制细胞增殖 [3]。在小鼠乳腺癌4T1细胞中，chloroquine diphosphate以时间和剂量依赖的方式抑制细胞增殖和存活，导致细胞凋亡 [2]。

在4T1细胞皮下异种移植小鼠模型中，chloroquine diphosphate显著抑制肿瘤生长和肿瘤细胞向肺部的转移，因而增加小鼠存活 [2]。在皮下注射colon26细胞的BALB/c小鼠中，chloroquine diphosphate与5-FU联合治疗通过增加凋亡细胞的比例，显著增强5-FU诱导的肿瘤生长抑制 [5]。

参考文献：
[1]. Gewirtz, D.A., An autophagic switch in the response of tumor cells to radiation and chemotherapy. Biochem Pharmacol, 2014. 90(3): p. 208-11.
[2]. Jiang, P.D., et al., Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother, 2010. 64(9): p. 609-14.
[3]. Choi, J.H., et al., Chloroquine enhances the chemotherapeutic activity of 5-fluorouracil in a colon cancer cell line via cell cycle alteration. APMIS, 2012. 120(7): p. 597-604.
[4]. Zhou, Z.R., et al., Poly(ADP-ribose) polymerase-1 regulates the mechanism of irradiation-induced CNE-2 human nasopharyngeal carcinoma cell autophagy and inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells. Oncol Rep, 2013. 29(6): p. 2498-506.
[5]. Sasaki, K., et al., Resistance of colon cancer to 5-fluorouracil may be overcome by combination with chloroquine, an in vivo study. Anticancer Drugs, 2012. 23(7): p. 675-82.