HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway

Liu, Weijun; Zhang, Zhenyong; Zhang, Yongxue; Chen, Xinju; Guo, Shikui; Lee, Yi; Xu, Yali; Ji, Chao; Zhang, Bi; Wang, Kunhua

doi:10.1080/15384047.2015.1017691

Cited by 70 publications

(71 citation statements)

References 28 publications

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“…Thus, the induction of autophagy has an important role in gemcitabine resistance of HIPC cells. Consistently, it has been reported that induced autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin (19) and mediates multi-drug resistance in osteosarcoma (20).…”

Section: Discussionsupporting

confidence: 51%

HMGB1‑mediated autophagy confers resistance to gemcitabine in hormone‑independent prostate cancer cells

et al. 2017

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Abstract. As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines. The results demonstrated that the autophagy markers were induced significantly in HIPC cells subsequent to gemcitabine treatment. Meanwhile, administration of gemcitabine to HIPC cells increased the expression of high mobility group box1 (HMGB1). Furthermore, the gemcitabine-induced autophagy response was attenuated in stable HIPC cells harboring HMGB1 shRNA. Notably, the HIPC cells stably transfected with HMGB1 shRNA or treated with autophagy inhibitors were more sensitive to gemcitabine compared with the control group. These data suggested that inhibition of HMGB1 increased the sensitivity to gemcitabine by decreasing autophagy response in HIPC cells. Overall, the present findings demonstrate a new mechanism for the resistance to gemcitabine in HIPC cell lines.

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Section: Discussionsupporting

confidence: 51%

HMGB1‑mediated autophagy confers resistance to gemcitabine in hormone‑independent prostate cancer cells

et al. 2017

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“…Additionally, HMGB proteins are subdivided into HMGB1, HMGB2, and HMGB3, all of which contain two HMG-box domains and a highly acidic Cterminal tail [10,11]. The current study found the expression levels of HMGB1 gene were significantly higher than that of the corresponding normal tissues in a variety of tumor tissues, including colorectal cancer, breast cancer, pancreatic cancer, melanoma, et al, which suggested that HMGB1 was involved in the occurrence and development of tumors [12][13][14][15][16]. Dong found that knockdown of the HMGB1 expression inhibited tumor growth and metastasis in human liver cancer through AKT-mediated regulation of Ki-67 and MMP-2 expression [17].…”

Section: Introductionmentioning

confidence: 42%

“…Chen had reported that HMGB1 was a novel biomarker and a therapeutic target for human ovarian cancer, which was associated with poor clinicopathologic features [19]. Liu et al had studied oxaliplatininduced drug resistance in human colorectal cancer cell lines HT29 and HCT116, and they found HMGB1-mediated autophagy modulated sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway [12]. Meanwhile, HMGB1, as one of the mediators in inflammatory reaction, was associated with tumorigenesis.…”

Section: Introductionmentioning

confidence: 97%

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Zhang

Wang

et al. 2015

Tumor Biol.

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Non-small cell lung cancer is commonly seen with higher morbidity and mortality. High-mobility group protein 1 (HMGB1) is a highly conserved nuclear protein, which is involved in multiple human diseases including cancers. However, the mechanisms of HMGB1 in non-small cell lung cancer remain unclear. The goal of the present study is to identify the relationship between HMGB1 and the progresssion of non-small cell lung cancer and investigate the molecular mechanism of HMGB1 in non-small lung cancer cell lines. Firstly, we detected the expression levels of HMGB1 by by real-time PCR and western blotting analysis, and the results demonstrated that HMGB1 was much higher expressed in non-small cell lung cancer cell lines, including A549, SPC-1-1, NCI-2170, SK-MES-1, and NCI-H1299, compared with that of WI-38. Next, 5 μM of adriamycin (AMD), 20 μM of cisplatin (DDP), and 50 μM of methotrexate (MTX) were used to treat A549 cells and SPC-A-1 cells for 48 h. The results showed that treatment with chemotherapy drugs significantly increased the levels of HMGB1 in A549 cells and SPC-A-1 cells. Moreover, the expression levels of HMGB1 increased in a time-dependent manner being treated with DDP. Then, the endogenous HMGB1 expression was successfully interferred with shRNA specific to HMGB1 in A549 and SPC-A-1 cells, which was detected by western blotting analysis. Then, the cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells were treated with increasing concentrations of cisplatin for 24, 48, and 72 h; cell viability were analyzed by MTT assay; and IC50 values were calculated. The results demonstrated that the expression level of HMGB1 in A549/DDP cells was much higher than that of A549 cells; moreover, transfection with HMGB1 shRNA in A549/DDP cells decreased the IC50 value of cisplatin in A549/DDP cells. The expression levels of autophagy-related proteins beclin-1 and LC3-II were significantly higher in A549/DDP cells or the A549 cells treated with chemotherapeutic drugs, compared with that in A549 cells. However, interference with endogenous HMGB1 obviously suppressed autophagy-related proteins and increased cell apoptosis rate and the expression of cleaved caspase-3 in A549/DDP cells. All of the data suggested that interference with the endogenous HMGB1 significantly inhibited cell autophagy and increased cell apoptosis of A549/DDP cells. Thus, the study on the resistance of chemotherapy drugs would provide a theoretical reference for clinical treatment of non-small cell lung cancer.

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“…3 In fact, the exact underlying molecular mechanism responsible for L-OHP resistance remains elusive up to now. Resistance to L-OHP is a complex process and several signaling pathways, such as the nuclear factor-kappa B (NF-κB) pathway, 4 the extracellular signal-regulated kinase (ERK)/Extracellular signal-regulated kinase (MEK) pathway, 5 and the protein kinase B (AKT/PKB) pathway, 6 have been involved in this phenomenon. Accumulating evidences demonstrate that activation of the AKT signaling pathway always leads to resistance to L-OHP induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer

et al. 2016

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Long noncoding RNAs act as crucial regulators in plenty of human cancers, yet their potential roles and molecular mechanisms in chemoresistance are poorly understood. This study showed that a novel lncRNA, long intergenic noncoding RNA 152 (Linc00152 ), promoted tumor progression and conferred resistance to oxaliplatin (L-OHP)-induced apoptosis in vitro and in vivo. It antagonized chemosensitivity through acting as a competing endogenous RNA to modulate the expression of miR-193a-3p, and then erb-b2 receptor tyrosine kinase 4 (ERBB4). Knockdown of ERBB4 in colon cancer cells decreased AKT phosphorylation, which resulted in decreased L-OHP resistance. Consistent with above findings, the specific AKT signaling inhibitor and activator were used, respectively, which demonstrated that Linc00152 contributed to L-OHP resistance at least partly through activating AKT pathway. Further studies indicated that Linc00152 was increased and appeared to be an independent prognostic factor for decreased survival and increased disease recurrence in stage II and III colon cancer patients undergoing L-OHP-based chemotherapy after surgery. Collectively, our findings established Linc00152 as a candidate prognostic indicator of outcome and drug responsiveness in colon cancer patients, and the involvement of competing endogenous RNAs mechanism in Linc00152/ miR-193a-3p/ERBB4/AKT signaling axis may provide a novel choice in the investigation of drug resistance.

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HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway

Cited by 70 publications

References 28 publications

HMGB1‑mediated autophagy confers resistance to gemcitabine in hormone‑independent prostate cancer cells

HMGB1‑mediated autophagy confers resistance to gemcitabine in hormone‑independent prostate cancer cells

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer

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