1.
CIP2A is associated with multidrug resistance in cervical adenocarcinoma by a P-glycoprotein pathway.
Liu, J, Wang, M, Zhang, X, Wang, Q, Qi, M, Hu, J, Zhou, Z, Zhang, C, Zhang, W, Zhao, W, et al
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;(2):2673-82
Abstract
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein. Here, we investigated its role in the formation of multidrug resistance (MDR) of cervical adenocarcinoma in vitro and in vivo. MTT assay showed that knockdown of CIP2A expression increased the drug sensitivity of HeLa and Dox-resistant HeLa cells (HeLa-Dox) to doxorubicin, cisplatin, and paclitaxel significantly, while overexpression of CIP2A decreased the sensitivity of HeLa cells to chemo-drugs dramatically. When treated with different chemotherapeutics, CIP2A and P-glycoprotein (P-gp) protein levels were increased in HeLa cells simultaneously. In accordance with it, knockdown or overexpression of CIP2A expression inhibited or increased the P-gp expression in the transcription level separately. The effects of CIP2A on P-gp expression was achieved partly through its regulation on the transcription factor E2F1. Moreover, the interference of CIP2A could decrease the P-gp protein activity elucidated by Rhodamine 123 (Rh123) efflux assay in HeLa and HeLa/Dox cells. In the in vivo level, confocal microscopy data demonstrated the strong co-localization of CIP2A and P-gp protein in HeLa cells, and CIP2A protein expression was significantly associated with that of P-gp in cervical adenocarcinoma tissues. Thus, CIP2A is involved in regulating multidrug resistance of cervical adenocarcinoma upon chemotherapy by enhancing P-gp expression through E2F1. CIP2A may be an attractive target in anticancer strategies to improve the effect of chemotherapy in cervical adenocarcinoma.
2.
High glucose promotes gastric cancer chemoresistance in vivo and in vitro.
Zhao, W, Chen, R, Zhao, M, Li, L, Fan, L, Che, XM
Molecular medicine reports. 2015;(1):843-50
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Abstract
The aim of the present study was to determine whether gastric cancer chemoresistance was increased under high glucose conditions by means of a clinical case study and experimental cytology. The expression of nicotinamide phosphoribosyltransferase (Nampt), silent information regulator 1 (sirt1), p53, p-glycoprotein (P-gp) and topoisomerase (topo)-IIα was evaluated in gastric cancer tissues and gastric cancer with diabetes tissues by immunohistochemistry. Subsequently, the survival time of the patients was assessed. For further investigation, the human gastric cancer cell line SGC7901 was subjected to different glucose concentrations and the aforementioned proteins were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Finally, cell sensitivity to chemotherapy treatment was examined in order to elucidate the role of high glucose in MDR. Positive expression of Nampt, Sirt1, p53, P-gp and Topo-IIα was observed to be higher in gastric cancer with diabetes patients compared with gastric cancer patients (P=0.01, 0.003, 0.0025, 0.016 and 0.336, respectively) with reduced survival time. Similar results were observed in SGC7901 cells. Additionally, cell proliferation rates of SGC7901 cells increased at glucose concentrations of 4,500 and 9,000 mg/l. Notably, the inhibition rates of 5-fluorouracil on cells decreased over 48 h when treated with 4,500 and 9,000 mg/l glucose compared with 1,000 mg/l. In conclusion, patients suffering from gastric cancer and diabetes exhibited greater negative effects, such as a poorer response to chemotherapy and had a lower survival time. High glucose conditions promoted gastric cancer cell proliferation and reduced susceptibility to chemotherapy drugs. These data provided a potential diagnostic and therapeutic strategy for gastric cancer chemoresistance.