Decreased drug resistance of bladder cancer using phytochemicals treatment

Kaohsiung Journal of Medical Sciences

Ching‐Wei Yang¹  Dah‐Shyong Yu²  Chia‐Lun Wu²  Cheng‐Ping Yu³  Jar‐Yi Ho³  Chun‐Jung Cho³ 

[1]Department of Urology Cheng‐Hsin General Hospital Taipei R.O.C.

[2]Division of Urology, Department of Surgery Tri‐Service General Hospital, National Defense Medical Center Taipei R.O.C.

[3]Graduate Institute of Pathology and Parasitology National Defense Medical Center Taipei R.O.C.

关键词: ABCC2 protein;    bladder cancer;    capsaicin;    gemcitabine resistance;    phytochemicals;   

DOI  :  10.1002/kjm2.12306

来源: DOAJ

【 摘 要 】

Abstract The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24‐GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24‐GCB cells in a dose‐dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24‐GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24‐GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24‐GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.

【 授权许可】

Unknown