Alkylglyceronephosphate Synthase (AGPS) Alters Lipid Signaling Pathways and Supports Chemotherapy Resistance of Glioma and Hepatic Carcinoma Cell Lines

Zhu, Yu; Liu, Xingjun; Yang, Ping; Zhao, Meng; Lv, Lixia; Zhang, Guodong; Wang, Qin; Zhang, Ling

doi:10.7314/apjcp.2014.15.7.3219

Cited by 30 publications

(24 citation statements)

References 28 publications

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“…For example, GST can acylate and inactivate cisplatin (16,17). The current study demonstrated that GST levels significantly increased in HepG2/DDP cells and significantly decreased subsequent to WEE1 silencing, suggesting that GST was also involved in WEE1-mediated drug resistance to cisplatin.…”

Section: Discussionsupporting

confidence: 49%

The role and mechanism of WEE1 on the cisplatin resistance reversal of the HepG2/DDP human hepatic cancer cell line

et al. 2015

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Abstract. Drug resistance to cisplatin with continuous drug treatment is one of the most common causes of chemotherapy failure in hepatic carcinoma. Accumulating evidence suggests that WEE1 G2 checkpoint kinase (WEE1) is involved in cisplatin resistance, which has been demonstrated to correlate with cancer initiation and progression. However, the role and molecular mechanism of WEE1 in the drug resistance of hepatic cancer remains unclear. In the present study, using the WEE-knockdown hepatic cancer cell line HepG2/DDP, the role of WEE1 and its molecular mechanism were investigated. It was demonstrated that silencing WEE1 expression resulted in an increased cisplatin sensitivity of HepG2/DDP, in addition to an increased rate of apoptosis and intracellular concentration of rhodamine 123. The expression levels of P-gp, MDR1, MRP1, LRP, BCL-2, survivin and GST in WEE1-silenced HepG2/DDP cells were significantly reduced, and phosphorylation levels of MEK and ERK were significantly downregulated. The results demonstrated that WEE1 negatively regulated the multidrug resistance potential of human hepatic cancer cells by modulating the expression of relevant drug resistance genes and the activity of the MEK/ERK pathway. Therefore, WEE1 may be a monitoring bio-marker for drug resistance, and a therapeutic target in hepatic cancer.

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Section: Discussionsupporting

confidence: 49%

The role and mechanism of WEE1 on the cisplatin resistance reversal of the HepG2/DDP human hepatic cancer cell line

et al. 2015

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“…Cells (0.3 ml; 1x10 6 /ml) were seeded onto a six-well microplate for 24 h and lysed using a lysate buffer (Beyotime Institute of Biotechnology);100 µg total cell lysate was the separated using 12% SDS-PAGE (Beyotime Institute of Biotechnology). Proteins were then transferred onto a polyvinylidene fluoride membrane (Millipore, Billerica, MA, USA) and blocked using 5% non-fat milk for 1 h at 4˚C.…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

“…Transforming growth factor (TGF)-β detection was performed using an ELISA kit (R&D Systems, Minneapolis, MN, USA) according to the manufacturer's instructions. In brief, cells (0.3 ml; 1x10 6 /ml) were seeded onto a six-well microplate for 24 h, the serum-free medium was replaced for and cells were incubated for a further 24 h. Absorbance was then determined using a microplate reader at 490 nm.…”

Section: Quantitative Pcr (Qpcr)mentioning

confidence: 99%

“…Therefore, multidrugresistance (MDR) reversal is significant in the development of tumor therapies. The major mechanisms underlying tumor MDR, include incerased drug excretion, decreased drug intracellular concentration and increased expression of antiapoptotic factors in tumor cells (6). Furthermore, the role of miR-10a in tumor cell apoptosis and drug resistance remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-β/Smad2/STAT3/STAT5 pathway

Sun

Chen

et al. 2015

Molecular Medicine Reports

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Abstract. Lung cancer is one of the primary causes of mortality worldwide and drug resistance is the key contributing factor which results in the failure of lung cancer chemotherapy. Previous studies have shown that microRNA (miR)-10a was involved in the reversal of cisplatin (DDP) resistance in numerous types of tumors; however, the underlying mechanism of action of this remains to be fully elucidated. In the present study, miR-10a silencing in human DDP-resistant lung cancer A549/DDP cells was demonstrated to improve DDP sensitivity, apoptosis, intracellular rhodamine-123 content as well as the expression and activity of caspase-3/8. In addition, miR-10a suppressed the cellular expression of P-glycoprotein, multi-drug resistance protein (MDR) 1, MDR-associated protein 1, RhoE, B cell lymphoma-2 and survivin in A549/DDP cells. Furthermore, miR-10a silencing inhibited the secretion of transforming growth factor (TGF)-β, phosphorylation of Sma-and Mad-related protein (Smad)2, signal transducer and activator of transcription (STAT)3 and STAT5, the transcriptional activity of hypoxia-inducible factor and eukaryotic translation initiation factor 4E in human lung cancer A549/DDP cell line. These results therefore indicated that miR-10a may be a potential target for improving the effectiveness of lung cancer chemotherapy via regulation of the TGF-β/Smad2/STAT3/STAT5 pathway.

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“…However, the molecular mechanism underlying this effect remains unclear. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters, also termed ATP-dependent transporters, have been implicated in drug resistance (23).…”

Section: Mir-155 Depletion Affects the Expression Of Drug Resistance-mentioning

confidence: 99%

Effect of miR-155 knockdown on the reversal of doxorubicin resistance in human lung cancer A549/dox cells

et al. 2015

Oncology Letters

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Abstract. Doxorubicin has been widely used in the treatment of cancer. However, acquired doxorubicin resistance severely hinders the application of the drug. In the present study, doxorubicin resistance was investigated in lung carcinoma. microRNA-155 (miR-155) was found to be upregulated in the doxorubicin-resistant A549/dox cell line. Suppression of miR-155 in this cell line considerably reversed doxorubicin resistance, and doxorubicin-induced apoptosis and cell cycle arrest were recovered. Furthermore, reverse transcription-polymerase chain reaction and western blot analysis revealed that miR-155 suppression downregulated the expression of multidrug resistance protein 1, multidrug resistance-associated protein 1, breast cancer resistance protein, glutathione S-transferase-π, Survivin and B-cell lymphoma 2, and upregulated the expression of caspase-3 and caspase-8. In addition, it was found that miR-155 suppression inhibited the activation of AKT and extracellular signal-regulated kinase. The transcriptional activity of nuclear factor-κB and activator protein-1 was also downregulated. In summary, the present results indicate that miR-155 may participate in doxorubicin resistance in lung carcinoma. The current study provides a novel target for lung carcinoma treatment.

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Alkylglyceronephosphate Synthase (AGPS) Alters Lipid Signaling Pathways and Supports Chemotherapy Resistance of Glioma and Hepatic Carcinoma Cell Lines

Cited by 30 publications

References 28 publications

The role and mechanism of WEE1 on the cisplatin resistance reversal of the HepG2/DDP human hepatic cancer cell line

The role and mechanism of WEE1 on the cisplatin resistance reversal of the HepG2/DDP human hepatic cancer cell line

MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-β/Smad2/STAT3/STAT5 pathway

Effect of miR-155 knockdown on the reversal of doxorubicin resistance in human lung cancer A549/dox cells

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