Department of Gynecology, Chifeng City Hospital, Chifeng City, Inner Mongolia, China.
Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1688-1696. doi: 10.26355/eurrev_202002_20343.
Ovarian cancer is prone to chemoresistance, leading to poor outcomes in patients. MicroRNA 1301 plays a regulatory role in multiple tumors. However, whether microRNA 1301 regulates cisplatin resistance in ovarian cancer cells remains unclear.
The ovarian cancer SKOV3 cell line and the human ovarian cancer cisplatin-resistant strain cell SKOV3/DDP were cultured in vitro and microRNA1301 expression was analyzed by Real time PCR. MicroRNA1301 mimics and microRNA 1301 were transfected into SKOV3/DDP, respectively followed by analysis of cell proliferation by MTT assay, cell invasion, expression of autophagy genes ATG5 and Beclin1 and EMT-related transcription factors Snail and Slug by Real time PCR, expression of NF-κB and E-cadherin and N-cadherin by Western blot.
MicroRNA 1301 expression was significantly increased in SKOV3/DDP cells compared with that in SKOV3 cells (p<0.05). MicroRNA1301 mimics transfection into SKOV3/DDP up-regulated microRNA1301 expression, promoted cell proliferation, and invasion, inhibited ATG5 and Beclin1 expression, and promoted Snail and Slug expression, decreased E-cadherin expression and increased N-cadherin and NF-κB expression, compared with the control group, the differences were statistically significant (p<0.05). MicroRNA1301 inhibitor transfection into SKOV3/DDP cells could down-regulate the expression of microRNA1301 and significantly reversed the above changes. Compared with the control group, differences were statistically significant (p<0.05).
Targeting microRNA1301 can inhibit the proliferation of cisplatin-resistant cells and the development of EMT in human ovarian cancer cells by inhibiting the NF-κB signaling pathway, thereby inhibiting the occurrence and development of drug-resistant ovarian cancer.
卵巢癌易发生化疗耐药,导致患者预后不良。微小 RNA 1301 在多种肿瘤中发挥调控作用。然而,微小 RNA 1301 是否调节卵巢癌细胞顺铂耐药尚不清楚。
体外培养卵巢癌 SKOV3 细胞系和人卵巢癌顺铂耐药株细胞 SKOV3/DDP,实时 PCR 分析微小 RNA1301 表达。分别将微小 RNA1301 模拟物和微小 RNA 1301 转染至 SKOV3/DDP 中,MTT 法分析细胞增殖,实时 PCR 分析自噬基因 ATG5 和 Beclin1 及 EMT 相关转录因子 Snail 和 Slug 表达,Western blot 分析 NF-κB 和 E-cadherin、N-cadherin 表达。
与 SKOV3 细胞相比,SKOV3/DDP 细胞中微小 RNA 1301 表达明显增加(p<0.05)。微小 RNA1301 模拟物转染至 SKOV3/DDP 中,上调微小 RNA1301 表达,促进细胞增殖和侵袭,抑制 ATG5 和 Beclin1 表达,促进 Snail 和 Slug 表达,降低 E-cadherin 表达,增加 N-cadherin 和 NF-κB 表达,与对照组相比,差异有统计学意义(p<0.05)。微小 RNA1301 抑制剂转染至 SKOV3/DDP 细胞可下调微小 RNA1301 表达,显著逆转上述变化。与对照组相比,差异有统计学意义(p<0.05)。
靶向微小 RNA1301 可通过抑制 NF-κB 信号通路抑制人卵巢癌细胞顺铂耐药细胞增殖和 EMT 的发展,从而抑制耐药性卵巢癌的发生和发展。