Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II

Huang, Can; Xu, Donghui; Qin, Xia; Wang, Peipei; Chen, Rong; Su, Yong

doi:10.1111/j.2042-7158.2012.01549.x

Cited by 66 publications

(52 citation statements)

References 28 publications

(53 reference statements)

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“…However, the regulatory mechanism underlying hypoxia-induced MDR in human laryngeal carcinoma cells remains to be identified. MDR1/P-gp is a member of the ABC-type transporter family and has been considered as a biofunctional regulator of MDR in a series of human tumor cells (19)(20)(21). In a previous study, it was demonstrated that the expression of MDR1/P-gp in human laryngeal cancer tissues was associated with malignant progression and metastasis (9).…”

Section: Discussionmentioning

confidence: 99%

Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells

Zhou

Huang

et al. 2016

Oncology Letters

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Abstract. In a previous study, it was demonstrated that hypoxia upregulated the multidrug resistance (MDR) of laryngeal cancer cells to chemotherapeutic drugs, with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp) expression also being upregulated. The present study aimed to investigate the role and mechanism of MDR1/P-gp on hypoxia-induced MDR in human laryngeal carcinoma cells. The sensitivity of laryngeal cancer cells to multiple drugs and cisplatin-induced apoptosis was determined by CCK-8 assay and Annexin-V/propidium iodide staining analysis, respectively. The accumulation of rhodamine 123 (Rh123) in the cells served as an estimate of drug accumulation and was evaluated by flow cytometry (FCM). MDR1/P-gp expression was inhibited using interference RNA, and the expression of the MDR1 gene was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. As a result, the sensitivity to multiple chemotherapeutic agents and the apoptosis rate of the hypoxic laryngeal carcinoma cells increased following a decrease in MDR1/P-gp expression (P<0.05). Additionally, FCM analysis of fluorescence intensity indicated that the downregulated expression of MDR1/P-gp markedly increased intracellular Rh123 accumulation (P<0.05). Such results suggest that MDR1/P-gp serves an important role in regulating hypoxia-induced MDR in human laryngeal carcinoma cells through a decrease in intracellular drug accumulation.

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Section: Discussionmentioning

confidence: 99%

Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells

Zhou

Huang

et al. 2016

Oncology Letters

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“…HIF-1α is an oxygenregulated subunit that mediates the essential function of HIF-1. The overexpression of HIF-1α may contribute to the pathogenesis of tumor resistance to chemotherapy (30,31). MRP1 is regarded as energy-dependent membrane efflux pumps and are widely believed to be transcriptionally regulated by HIF-1α in multiple human tumors (32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines

Ling

Feng

et al. 2014

Oncology Reports

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Abstract.Metformin is an oral anti-hyperglycemic agent of the biguanide family, which is used first-line for type II diabetes with few side-effects. A recent epidemiological study that included 1,828 potential intrahepatic cholangiocarcinoma (ICC) patients showed that metformin use was significantly associated with a 60% reduction in ICC risk in diabetic patients, demonstrating the potential value of metformin in ICC management. In the present study, we firstly showed that metformin exhibited a dose-and time-dependent anti-proliferation effect on ICC cell lines, by mechanisms including apoptosis induction and cell cycle arrest. Metformin targeted the AMPK/mTORC1 pathway in ICC cells. Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As 2 O 3 by targeting the AMPK/mTOR/ HIF-1α/MRP1 pathway and ERK. As it is an inexpensive and widely used antidiabetic drug without severe adverse effects, metformin may be a prospective chemotherapeutic agent or a chemosensitizer in future ICC treatment. IntroductionMetformin, a first-line oral anti-type II diabetes agent used worldwide, displays an antitumorigenesis effect, according to recent epidemic studies (1-3). As compared to insulin or sulfonylureas administration, metformin use may markedly reduce the cancer risk in patients with type II diabetes. Recent studies have confirmed the anti-proliferation effect on various human cancer cell types, such as pancreas (4), prostate (5), breast (6), stomach (7) and liver (8). Metformin inhibits the pro-proliferation effect of insulin receptor-and IGF receptor-dependent signaling by reducing insulin resistance. Furthermore, metformin activates AMP-activated protein kinase (AMPK) and subsequently inhibits activation of mammalian target of rapamycin (mTOR) to prevent proliferation of tumor cells, and activates p53 protein-inducing cell cycle arrest of tumor cells. Several studies have indicated that metformin can potentiate the effect of chemotherapeutic agents or reverse drug resistance in cancer cells (8-10). However, the mechanism of the anti-cancer effects of metformin remains unclear.A recent epidemiological study that included 1,828 potential intrahepatic cholangiocarcinoma (ICC) patients described that metformin use was significantly associated with a 60% reduction in ICC risk in diabetic patients (11). Cholangiocarcinoma (CC)categorized as intrahepatic and extrahepatic cholangiocarcinoma (ECC) is highly lethal. ICC is the second most common type of primary liver cancer and its incidence and mortality rates have been rising in recent decades (12-15). Less than 30% of patients with ICC have the opportunity to have radical operation at diagnostic presentation. Apart from radical operation, some treatment approaches such as systemic chemotherapy, transarterial chemoembolization and radiofrequency ablation may be applied at advanced stages of ICC; however, none of the approaches can significantly improve the prognosis of ICC. Thus, new treatment strategies are needed ...

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“…Astragalus polysaccharides have been reported to be potent to enhance antitumor effects of adriamycin in H22 hepatocarcinoma by upregulating IL1α, IL2, IL6, and TNFα, downregulating IL10 and multidrug resistance protein 1 (MDR1) [199] . Astragaloside Ⅱ, another component from HuangQi (Astragalus membranaceus), is effective to increase 5Fu cytotoxicity toward 5Fu resistant Bel7402/Fu cells accompanied by down regulation of Pgp (Pglycoprotein), phosphorylation of ERK1/2, p38 and JNK [200] . Green tea catechins have been reported to effec tively inhibit MDR1 expression, increase intracellular doxorubicin (DOX) accumulation and enhance DOX induced cell killing activities against BEL7404/DOX cells [201] .…”

Section: Reversal Of Drug Resistancementioning

confidence: 99%

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Wang

2015

WJH

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and other TCM syndromes (Zheng). Modern treatments such as surgery, transarterial chemoembolization (TACE) and high intensity focus ultrasound treatment would influence the manifestation of TCM syndromes. Herbs with traditional efficacy of tonifying Qi, blood and Yin, soothing liver-Qi stagnation, clearing heat and detoxifying and dissolving stasis, have been demonstrated to be potent to prevent hepatocarcinogenesis. TCM has been widely used in all aspects of integrative therapy in hepatocarcinoma, including surgical resection, liver transplantation, TACE, local ablative therapies and even as monotherapy for middle-advanced stage hepatocarcinoma. Clinical practices have confirmed that TCM is effective to alleviate clinical symptoms, improve quality of life and immune function, prevent recurrence and metastasis, delay tumor progression, and prolong survival time in hepatocarcinoma patients. The effective mechanism of TCM against hepatocarcinoma is related to inducing apoptosis, autophagy, anoikis and cell senescence, arresting cell cycle, regulating immune function, inhibiting metastasis and angiogenesis, reversing drug resistance and enhancing effects of chemotherapy. Along with the progress of research in this field, TCM will contribute more to the prevention and treatment of hepatocarcinoma. AbstractTraditional Chinese medicine (TCM) has played a positive role in the management of hepatocarcinoma. Hepatocarcinoma patients may present Qi-stagnation, damp-heat, blood stasis, Qi-deficiency, Yin-deficiency REVIEWSubmit a

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Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II

Abstract: The results suggested that Astragaloside II is a potent MDR reversal agent and may be a potential adjunctive agent for hepatic cancer chemotherapy.

Cited by 66 publications

References 28 publications

Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells

Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells

Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

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