Antitumor Activity of Chloroquine in Combination with Cisplatin in Human Gastric Cancer Xenografts

Zhang, Huiqing; Fang, Nian; Liu, Xiaomei; Xiong, Shuping; Liao, Yuqian; Jin, Wenjian; Song, Rongfeng; Wan, Yiye

doi:10.7314/apjcp.2015.16.9.3907

Cited by 22 publications

(14 citation statements)

References 20 publications

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“…For example, the upregulation of ATG5 was reported to be associated with chemoresistance [ 40 ]. Moreover, multiple publications demonstrate that inhibiting autophagy potentiates the cytotoxic effects of DNA damaging chemotherapeutic drugs [ 41 – 44 ]. Interestingly, Yang and colleagues observed contradictory phenomena as they published that 5FU possibly suppresses a microRNA which negatively regulates autophagy via Beclin1, which results in increased autophagic flux and autophagic cell death [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas

et al. 2018

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Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resistance. We aimed to assess the impact of autophagy on chemotherapy response in EAC, with a special focus on paclitaxel. Responsiveness of EAC cell lines, OE19, FLO-1, OE33 and SK-GT-4, to paclitaxel was assessed using Alamar Blue assays. Autophagic flux upon paclitaxel treatment in vitro was assessed by immunoblotting of LC3B-II and quantitative assessment of WIP1 mRNA. Immunohistochemistry for the autophagy markers LC3B and p62 was applied on tumor tissue from 149 EAC patients treated with neoadjuvant chemotherapy, including pre- and post-therapeutic samples (62 matched pairs). Tumor response was assessed by histology. For comparison, previously published data on 114 primary resected EAC cases were used. EAC cell lines displayed differing responsiveness to paclitaxel treatment; however this was not associated with differential autophagy regulation. High p62 cytoplasmic expression on its own (p ≤ 0.001), or in combination with low LC3B (p = 0.034), was associated with nonresponse to chemotherapy, regardless of whether or not the regiments contained paclitaxel, but there was no independent prognostic value of LC3B or p62 expression patterns for EAC after neoadjuvant treatment. p62 and related pathways, most likely other than autophagy, play a role in chemotherapeutic response in EAC in a clinical setting. Therefore p62 could be a novel therapeutic target to overcome chemoresistance in EAC.

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Section: Discussionmentioning

confidence: 99%

A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas

et al. 2018

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“…In the second scenario, autophagy acts as an oncogenetic pathway that favors tumor cell survival. The addition of autophagy inhibitor, such as chloroquine and bafilomycin A1, sensitizes the cytotoxicity of anti-cancer drugs in gastric cancer cells [ 63 - 68 ], indicating the autophagy inhibitor might be a favorable candidate for the chemotherapy of gastric cancer. The specific mechanism underlying the pro-survival function of autophagy remains largely unknown.…”

Section: Autophagy In Oncogenesis Of Gastric Cancermentioning

confidence: 99%

Functional role of autophagy in gastric cancer

Qian

Yang

2016

Oncotarget

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Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. Perturbations in autophagy are found in gastric cancer. In host gastric cells, autophagy can be induced by Helicobacter pylori (or H. pylori) infection, which is associated with the oncogenesis of gastric cancer. In gastric cancer cells, autophagy has both pro-survival and pro-death functions in determining cell fate. Besides, autophagy modulates gastric cancer metastasis by affecting a wide range of pathological events, including extracellular matrix (ECM) degradation, epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, and tumor microenvironment. In addition, some of the autophagy-related proteins, such as Beclin 1, microtubule-associated protein 1 light chain 3 (MAP1-LC3), and p62/sequestosome 1 (SQSTM1) have certain prognostic values for gastric cancer. In this article, we review the recent studies regarding the functional role of autophagy in gastric cancer.

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“…Current therapeutic strategies of treating intermediate and advanced liver cancer use a combination of cisplatin and other chemotherapy agents, including paclitaxel, gemcitabine and cyclophosphamide. However, the mechanism underlying their anticancer or apoptosis-promoting effects remains unclear and numerous studies have indicated that autophagy may serve a potential role in the anticancer effect of chemotherapeutic reagents ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of ginkgol C17:1 on cisplatin‑induced autophagy and apoptosis in HepG2 cells

Liu

Xiaoming

et al. 2017

Oncol Lett

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Previous studies have demonstrated that ginkgol C17:1 significantly inhibits human liver cancer cells and enhances the anticancer activity of cisplatin in vivo and in vitro. However, the mechanism and biological function of ginkgol C17:1 on cells undergoing chemotherapy remain unclear. The aim of the present study was to determine the antitumor activity and mechanism of ginkgol C17:1 in combination with cisplatin in human hepatoblastoma HepG2 cells. The green fluorescent protein (GFP)-light chain 3 (LC3) adenovirus was transfected into HepG2 cells and autophagic flux was determined using fluorescence microscopy. Western blot analysis was also conducted to measure the expression of proteins associated with apoptosis, autophagy and their associated signaling pathways. Compared with the control group, autophagic flux and nucleus aberration rates were significantly increased (P<0.05), and the expression of proteins associated with autophagy and apoptosis were increased in the groups treated with cisplatin or ginkgol C17:1, respectively. However, following co-treatment with ginkgol C17:1 and cisplatin, the autophagic flux and the expression of autophagy proteins decreased; however, the nucleus aberration rate and apoptosis protein expression significantly increased (P<0.05) compared with the group treated with cisplatin alone. Additionally, the signaling pathways of autophagy and apoptosis were also activated following treatment with cisplatin, alone and in combination with ginkgol C17:1. Taken together, these results indicate that ginkgol C17:1 inhibits cisplatin-induced autophagy via AMP-activated protein kinase/ULK1signaling and increases cisplatin-induced apoptosis in HepG2 cells via the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway.

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Antitumor Activity of Chloroquine in Combination with Cisplatin in Human Gastric Cancer Xenografts

Cited by 22 publications

References 20 publications

A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas

A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas

Functional role of autophagy in gastric cancer

Effects of ginkgol C17:1 on cisplatin‑induced autophagy and apoptosis in HepG2 cells

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