MEK inhibitor enhances sensitivity to chemotherapeutic drugs in multidrug resistant hepatocellular carcinoma cells

Meng, Qingliang; He, Xiaoqi; Xie, Guangwei; Tian, Qingzhong; Shu, Xuefeng; Jin, Li; Xiao, Yong

doi:10.3892/ol.2017.6494

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…The study by Fang et al (28) reported that downregulation of UBC9 increased the sensitivity of HCC cells to doxorubicin. In addition, Meng et al (29) indicated that MEK inhibitors enhance the sensitivity of multidrug resistant HCC cells to chemotherapeutic drugs. Previous studies further reported that norcantharidin suppresses proliferation, inhibits invasion and metastasis, and induces apoptosis in HCC cells, which is a potential treatment of HCC (30,31).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of interferon‑stimulated gene 15 affects the sensitivity of hepatocellular carcinoma cells to norcantharidin

et al. 2019

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Interferon-stimulated gene 15 (ISG15) serves a crucial role in hepatocellular carcinoma (HCC) progression. The present study explored the effect of ISG15 knockdown on the sensitivity of HCC cells to norcantharidin. The expression of ISG15 in HCC tissues and cell lines was assessed by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Pearson's χ 2 test was conducted to analyze the correlation between the clinicopathological features and ISG15 expression of patients with HCC. In addition, HCC cells were transfected with small interfering RNA against ISG15, ISG15 overexpression plasmid or respective negative controls. Cell proliferation, clonogenic ability and apoptosis were examined by Cell Counting Kit-8, colony formation and Annexin V/propidium iodide staining assays, respectively. Protein expression was assessed by western blot analysis. The results revealed that ISG15 was overexpressed in HCC tissues, and that ISG15 expression was positively correlated with HCC differentiation and metastasis. Downregulation of ISG15 increased the sensitivity of HCC cells to norcantharidin, and norcantharidin treatment reversed the tumor-promoting effects of ISG15 overexpression exerted in HCC cells. Furthermore, the expression levels of apoptosis-associated proteins were regulated by ISG15 and norcantharidin. Taken together, the observed increase in the sensitivity of HCC cells to norcantharidin was facilitated by ISG15 knockdown and may provide novel insights for HCC therapy.

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Section: Discussionmentioning

confidence: 99%

Knockdown of interferon‑stimulated gene 15 affects the sensitivity of hepatocellular carcinoma cells to norcantharidin

et al. 2019

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“…However, chemoresistance remains a major barrier for chemotherapeutic agents, prompting considerable research on suitable treatments for HCC (Asghar & Meyer, ). MAPKs play an important role in regulating growth, metastasis, apoptosis, and chemoresistance (Meng et al, ). Previous research has shown that U0126, a highly selective inhibitor of both MEK1 and MEK2 (types of MAPK/Erk kinases), can enhance sensitivity to chemotherapeutic drugs in the HepG2/ADM cell model of multidrug resistance (Meng et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…MAPKs play an important role in regulating growth, metastasis, apoptosis, and chemoresistance (Meng et al, 2017). Previous research has shown that U0126, a highly selective inhibitor of both MEK1 and MEK2 (types of MAPK/Erk kinases), can enhance sensitivity to chemotherapeutic drugs in the HepG2/ADM cell model of multidrug resistance (Meng et al, 2017). Accordingly, to better understand the causes of chemoresistance, this study focused on the effects of exposure to nontoxic concentrations of AlCl 3 on 5-FU chemoresistance in HCC (HepG2) cells and attempted to elucidate the underlying mechanisms.…”

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confidence: 99%

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Aluminum chloride causes 5‐fluorouracil resistance in hepatocellular carcinoma HepG2 cells

Cui

Zakki

et al. 2019

Journal Cellular Physiology

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Chemoresistance is one of the major obstacles in chemotherapy-based hepatocellular carcinoma (HCC) intervention. Aluminum (Al) is an environmental pollutant that plays a vital role in carcinogenesis, tumorigenesis, and metastasis. However, the effect of Al on chemoresistance remains unknown. 5-Fluorouracil (5-FU) is a widely used antitumor drug. Therefore, we investigated the effects of aluminum chloride (AlCl 3 ) on the chemoresistance of HepG2 cells to 5-FU and explored the underlying mechanisms of these effects. The results demonstrated that AlCl 3 pretreatment attenuated 5-FUinduced apoptosis through Erk activation and reversed 5-FU-induced cell cycle arrest by downregulating p-Chk2 Thr68 levels. In addition, AlCl 3 markedly increased the levels of proteins associated with cell migration, such as MMP-2 and MMP-9. Further investigation demonstrated that an Erk inhibitor (U0126) reversed the AlCl 3 -induced decrease in apoptosis, enhancement of cell cycle progression, promotion of cell migration, and attenuation of oxidative stress. In summary, AlCl 3 induced chemoresistance to 5-FU in HepG2 cells. The present study suggests a potential influence of AlCl 3 on 5-FU therapy. These findings may help others to understand and properly address the resistance of HCC to chemotherapeutic agents.

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“…6) ABCB1 is a target of the Ras/Raf signaling pathway, suppression of p38, ERK or JNK pathways enhanced sensitivity to chemotherapeutic drugs in multidrug resistant tumor cells. [7][8][9][10] Paris polyphylla var. yunnanensis (Franch.)…”

Section: Introductionmentioning

confidence: 99%

Total Saponins from <i>Paris forrestii</i> Reverse Multidrug Resistance of MCF-7/ADM Cells by Suppression of P-gp <i>via</i> ERK Signaling Pathway

Chai

Yuan

Zhu

et al. 2020

Biological & Pharmaceutical Bulletin

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Our previous study demonstrated that the total saponins from Paris forristii (PCT3)had obvious inhibitory effect on the proliferation of adriamycin-resistant human breast adenocarcinoma cells (MCF-7/ADM), this effect was significantly stronger than that in parental cells (MCF-7). This study was designed to test the reversal effect of PCT3 on MCF-7/ADM cells and to understand its mechanism of action. Results demonstrated that low cytotoxic concentrations of PCT3 (0.3, 1 and 3 µg/ml) reversed resistance of MCF-7/ADM cells to ADM, DDP and 5-FU, with reversal fold of 16.4, 19.5 and 31.7 for ADM, 1.6, 1.4 and 1.4 for DDP, 1.7, 1.8 and 5.6 for 5-FU, respectively. Moreover, PCT3 significantly increased the accumulation of ADM and Rh123 in MCF-7/ADM cells, suggesting that PCT3 may act by affecting the function of drug efflux pump P-gp, which is encoded by MDR1 gene. Both MDR1 gene and P-gp protein expression was downregulated by PCT3 treatment. Further results demonstrated that p38MAPK and ERK pathway was remarkably activated in MCF-7/ADM cells, inhibition of p38 or ERK attenuated P-gp expression. While, only the phosphorylation level of ERK was downregulated by PCT3, indicating that PCT3 sensitized P-gp overexpressed MCF-7/ADM cells to ADM via inhibition of ERK signaling pathway.

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MEK inhibitor enhances sensitivity to chemotherapeutic drugs in multidrug resistant hepatocellular carcinoma cells

Cited by 6 publications

References 22 publications

Knockdown of interferon‑stimulated gene 15 affects the sensitivity of hepatocellular carcinoma cells to norcantharidin

Knockdown of interferon‑stimulated gene 15 affects the sensitivity of hepatocellular carcinoma cells to norcantharidin

Aluminum chloride causes 5‐fluorouracil resistance in hepatocellular carcinoma HepG2 cells

Total Saponins from <i>Paris forrestii</i> Reverse Multidrug Resistance of MCF-7/ADM Cells by Suppression of P-gp <i>via</i> ERK Signaling Pathway

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