Regulation of SIRT1 in acquired resistance of TKIs in non-small cell lung cancer
LI Guifang1 YUAN Xiang2 LIU Yiwen2 MA Mingyang1 SUN Jiangtao3
1.First Affiliated Hospital, College of Clinical Medicine of He′nan University of Science and Technology, He′nan Province, Luoyang 471003, China;
2.He′nan Key Laboratory of Cancer Epigenetics Cancer Institute, the First Affiliated Hospital of He′nan University of Science and Technology, He′nan Province, Luoyang 471003, China;
3.The First Affiliated Hospital of He′nan University of Science and Technology, He′nan Province, Luoyang 471003, China
Abstract：Objective To analyze the regulation of histone deacetylase SIRT1 in stem cell-like properties of non-small cell lung cancer. Methods The percentage of tumor stem cells was detected by flow cytometry in PC-9 and PC-9-GR cell lines; IC50 was detected by CCK8; SIRT1 mRNA expression was detected by qPCR; SIRT1 protein expression was detected by Western blot; the experiments of cell suspension cloning into spheres was used to detect the capability of sphere-forming of different groups. Results The drug-resistant cell line PC-9-GR was successfully established. The IC50, ALDHbright tumor stem cell percentage, SIRT1 protein expression and SIRT1 mRNA expression of PC-9-GR were higher than those of PC-9 (P < 0.05). The experiments of cell suspension cloning into spheres found that PC-9-GR was significantly higher than PC-9 (P < 0.05), and the effect of PC-9-GR on the capability of sphere-forming was not statistically significant after the application of Gefitinib (P > 0.05). After the combination of SIRT1 specific inhibitor TV6 and double drug combination, the capability of sphere-forming of the two cell lines was significantly lower than that of the control group (P < 0.05). Conclusions Acquired resistance to tyrosine kinase inhibitors in non-small cell lung cancer is closely related to the enrichment of ALDH1+ labeled cancer stem cells by tyrosine kinase inhibitors. Histone deacetylase SIRT1 plays an important role in maintaining the stem of these cancer stem cells. Its inhibition of SIRT1 targeting tumor stem cells may help delay the acquired resistance of tyrosine kinase inhibitors.
李桂芳1 原翔2 刘怡文2 马名扬1 孙江涛3. SIRT1在非小细胞肺癌TKIs获得性耐药中的调控作用[J]. 中国医药导报, 2019, 16(16): 4-7,12.
LI Guifang1 YUAN Xiang2 LIU Yiwen2 MA Mingyang1 SUN Jiangtao3. Regulation of SIRT1 in acquired resistance of TKIs in non-small cell lung cancer. 中国医药导报, 2019, 16(16): 4-7,12.
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2019, Vol. 16 
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