Abstract:Objective: To investigate enhancement of silencing BRM gene by siRNA on the sensitivity of human pancreatic cancer cell line to gemcitabine. Methods: Panc-1 cells from human pancreatic cancer in vitro were cultured. Negative control NC and BRM siRNA were transfected into Panc-1 cells cultured in vitro. The expression of BRM in Panc-1 cells was detected by RT-PCR and Western Blot, so as to identify the silencing effect of BRM-specific siRNA. Different concentrations of gemcitabine were used to detect the cell proliferation rate, and the half-inhibitory concentration (IC50) was calculated. The apoptosis rate of Panc-1 cells and the protein expression levels of JAK2, STAT3, p-STAT3 and Survivin in Panc-1 cells were detected. Results: The expression of BRM mRNA and protein in Panc-1 cells of BRM siRNA group was significantly lower than that of blank control group and NC control group (P<0.05). The inhibition rate of gemcitabine on Panc-1 cell proliferation in BRM siRNA group was higher than that in blank control group and NC control group (P<0.05); The IC50 of the blank control group, the NC control group and the BRM siRNA group were 5.18 ug/mL, 5.05 ug/mL and 3.05 ug/mL, respectively; After gemcitabine treatment with the final concentration of 3.0ug/mL, the apoptotic rate of Panc-1 cells in BRM siRNA group was significantly higher than that in blank control group and NC control group (P<0.05), STAT3 was not significantly changed (P>0.05), while the expression of JAK2, p-STAT3 and Survivin protein was significantly decreased (P<0.05). Conclusion: Silencing BRM expression by siRNA can increase the sensitivity of Panc-1 cells to citrate, which may be related to the activation of JAK2/STAT3 pathway by BRM to promote pancreatic cancer growth and drug resistance.
屈涛, 张弘刚, 汤海舰, 刘伟. siRNA沉默BRM增强胰腺癌细胞对吉西他滨敏感性的作用机制研究[J]. 河北医学, 2019, 25(10): 1620-1623.
QU Tao, ZHANG Honggang, et al. Study on the Mechanism of siRNA Silencing BRM Enhancing the Sensitivity of Pancreatic Cancer Cells to Gemcitabine. HeBei Med, 2019, 25(10): 1620-1623.
[1] 项金峰,施思,梁丁孔,等.2015年胰腺癌研究及诊疗前沿进展[J].中国癌症杂志,2016,26(4):281~289. [2] 朱飞,魏宇峰,王增,等.吉西他滨相关血小板减少对晚期非小细胞肺癌患者生存时间的影响[J].中国药师,2018,21(3):429~431. [3] Shinozuka K, Tang H , Jones RB , et al. Impact of polymorphic variations of gemcitabine metabolism, DNA damage repair and drug-resistance genes on the effect of high-dose chemotherapy for relapsed or refractory lymphoid malignancies[J]. Biol Blood Marrow Transplant, 2016, 22(5):843~849. [4] Tang Y, Wang J, Lian Y, et al. Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer[J]. Molecular Cancer, 2017, 16(1):42. [5] Yu Y, Cheng D, Parfrey P, et al. Two functional indel polymorphisms in the promoter region of the Brahma gene (BRM) and disease risk and progression-free survival in colorectal cancer[J]. PLOS ONE, 2018, 13(6):e0198873. [6] Marquez-Vilendrer SB, Rai SK, Gramling SJ, et al. Loss of the SWI/SNF ATPase subunits BRM and BRG1 drives lung cancer development[J]. Oncoscience, 2016, 3(11-12):322~336. [7] Park K, Cho EK, Bello M, et al. Efficacy and safety of first-Line necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin in east asian patients with stage IV squamous non-small cell lung cancer: a subgroup analysis of the phase 3, open-label, randomized SQUIRE study[J]. Cancer Res Treat, 2017, 49(4):937~946. [8] Karampelas T , Skavatsou E , Argyros O , et al. Gemcitabine based peptide conjugate with improved metabolic properties and dual mode of efficacy[J]. Mol Pharm, 2017, 14(3):674~685. [9] Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial[J]. Lancet, 2017, 389(10073):1011~1024. [10] Raab JR, Runge JS, Spear CC, et al. Co-regulation of transcription by BRG1 and BRM, two mutually exclusive SWI/SNF ATPase subunits[J]. Epigenetics Chromatin, 2017, 10(1):62~73. [11] Priedigkeit N, Hartmaier RJ, Chen Y, et al. Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases[J]. JAMA Oncol, 2017, 3(5):666~671. [12] 雷越,万婕,文韬宇,等.siRNA沉默FOXM1基因表达对人鼻咽癌细胞增殖、凋亡及化疗敏感性的影响[J].肿瘤,2018,38(1):25~34. [13] Zhu H , Liu W , Cheng Z , et al. Targeted delivery of siRNA with pH-Responsive hybrid gold nanostars for cancer treatment[J]. Int Mol Sci, 2017, 18(10):2029~2038. [14] Zhang Z , Wang F , Du C , et al. BRM/SMARCA2 promotes the proliferation and chemoresistance of pancreatic cancer cells by targeting JAK2/STAT3 signaling[J]. Cancer Lett, 2017,402:213~224. [15] Doi T, Ishikawa T, Okayama T, et al. The JAK/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines[J]. Oncol Rep, 2017, 37(3):1545~1554.