Compound A attenuates toll-like receptor 4-mediated paclitaxel resistance in breast cancer and melanoma through suppression of IL-8

BMC Cancer
Rochanawan SootichoteChanitra Thuwajit

Abstract

Paclitaxel (PTX) is a potent anti-cancer drug commonly used for the treatment of advanced breast cancer (BCA) and melanoma. Toll-like receptor 4 (TLR4) promotes the production of pro-inflammatory cytokines associated with cancer chemoresistance. This study aims to explore the effect of TLR4 in PTX resistance in triple-negative BCA and advanced melanoma and the effect of compound A (CpdA) to attenuate this resistance. BCA and melanoma cell lines were checked for the response to PTX by cytotoxic assay. The response to PTX of TLR4-transient knockdown cells by siRNA transfection was evaluated compared to the control cells. Levels of pro-inflammatory cytokines, IL-6 and IL-8, and anti-apoptotic protein, XIAP were measured by real-time PCR whereas the secreted IL-8 was quantitated by ELISA in TLR4-transient knockdown cancer cells with or without CpdA treatment. The apoptotic cells after adding PTX alone or in combination with CpdA were detected by caspase-3/7 assay. PTX could markedly induce TLR4 expression in both MDA-MB-231 BCA and MDA-MB-435 melanoma cell lines having a basal level of TLR4 whereas no significant induction in TLR4-transient knockdown cells occurred. The siTLR4-treated BCA cells revealed more dead cells after PTX tr...Continue Reading

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Feb 6, 2019·International Journal of Molecular Medicine·Cheng-Lin WuLi-Jun Zhou
Sep 4, 2018·Clinical and Translational Medicine·Weilong ChenSuling Liu
Jan 12, 2021·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Luciana MoscaGianni Colotti
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Sep 21, 2021·Frontiers in Oncology·Concetta SaponaroAnita Mangia

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Methods Mentioned

BETA
PCR
transfection
electrophoresis
ELISA

Software Mentioned

IncuCyte ZOOM
ImageJ®
Lightcycler® 480

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