Knockdown of KLK11 reverses oxaliplatin resistance by inhibiting proliferation and activating apoptosis via suppressing the PI3K/AKT signal pathway in colorectal cancer cell

OncoTargets and Therapy
Yiyi ZhangXingrong Lu

Abstract

Kallikrein 11 (KLK11) plays a crucial role in drug-resistance to oxaliplatin (L-OHP) in the treatment of metastatic colorectal cancer (mCRC). The study aimed to investigate the role of KLK11 in chemoresistance, and to clarify the mechanism underlying reverse of L-OHP resistance by knockdown of KLK11. Resistance to oxaliplatin was induced in HCT-8 (HCT-8/L-OHP) colorectal adenocarcinoma cell lines by exposing cells to increasing concentrations of L-OHP. MTT, RT-qPCR, and Western blot were used to evaluate the resistance to L-OHP. We then knocked down KLK11 in HCT-8/L-OHP cells to explore the mechanism through which KLK11 reverses L-OHP resistance. The mRNA and protein expression of KLK11 in tissues from mCRC patients were detected by RT-qPCR and immunohistochemistry. The drug resistance index (RI) of HCT-8/L-OHP cell line to L-OHP, 5-Fluorouracil (5-FU), Irinotecan (CPT-11), Vincristine (VCR) and Cis-diamminedichloroplatinum (CDDP) were 10, 5.35, 3.23, 1.28, and 6.64, respectively. Increased expression of multi-drug resistant genesABCC1,ABCB1,GSTP1andERCC1were detected in HCT-8/L-OHP cell line. Moreover, the activated PI3K/AKT pathway was related to L-OHP-resistance. Knockdown ofKLK11in HCT-8/L-OHP cell reversed L-OHP-resistance...Continue Reading

Citations

Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Saeranee SiriphakSiriporn Proungvitaya

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Methods Mentioned

BETA
PCR
transfection
protein assay
electrophoresis

Software Mentioned

SPSS

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