Fatty Acid Binding Protein 6 Inhibition Decreases Cell Cycle Progression, Migration and Autophagy in Bladder Cancers.

Chieh-Hsin Lin,Yu-Ling Tsai,Sheng-Tang Wu,Yu-Chen Cheng,Chih-Ying Changchien,Hsin-Han Chang,Ying Chen,Wen-Chiuan Tsai,Hisao-Hsien Wang,Chien-Rui Lai

doi:10.3390/ijms23042154

Abstract

Bladder cancer (BC) has a high recurrence rate worldwide. The aim of this study was to evaluate the role of fatty acid binding protein 6 (FABP6) in proliferation and migration in human bladder cancer cells. Cell growth was confirmed by MTT and colony formation assay. Western blotting was used to explore protein expressions. Wound healing and Transwell assays were performed to evaluate the migration ability. A xenograft animal model with subcutaneous implantation of BC cells was generated to confirm the tumor progression. Knockdown of FABP6 reduced cell growth in low-grade TSGH-8301 and high-grade T24 cells. Cell cycle blockade was observed with the decrease of CDK2, CDK4, and Ki67 levels in FABP6-knockdown BC cells. Interestingly, knockdown of FBAP6 led to downregulation of autophagic markers and activation of AKT-mTOR signaling. The application of PI3K/AKT inhibitor decreased cell viability mediated by FABP6-knockdown additionally. Moreover, FABP6-knockdown reduced peroxisome proliferator-activated receptor γ and retinoid X receptor α levels but increased p-p65 expression. Knockdown of FABP6 also inhibited BC cell motility with focal adhesive complex reduction. Finally, shFABP6 combined with cisplatin suppressed tumor growth in vivo. These results provide evidence that FABP6 may be a potential target in BC cells progression.

Highlights

Bladder cancer (BC) is the 10th most-commonly diagnosed cancer worldwide, with high mortality and recurrence rates [1]
Corresponding immunohistochemistry sections had enhanced fatty acid binding protein 6 (FABP6) staining in both low- and high- grade urothelial carcinomas (UC)
FABP6 expression in different BC cell lines was analyzed by Western blotting (Figure 1C)

Summary

Introduction

Bladder cancer (BC) is the 10th most-commonly diagnosed cancer worldwide, with high mortality and recurrence rates [1]. BC can be divided into non-muscle invasive BC (NMIBC, Ta and T1) and muscle invasive BC (MIBC, T2 and T3). 75% of BC patients are considered as NMIBC—the most prevalent type of BC. Transurethral resection of bladder tumor (TURBT) followed by immediate postoperative instillation of intravesical chemotherapy adjuvant intravesical immunotherapy (BCG) or chemotherapy is the standard of care for NMIBC. Chemotherapy with gemcitabine and cisplatin is commonly used in muscle-invasive BC [2]. Despite state-of-the-art surgical techniques and neoadjuvant chemotherapy, the five-year survival rate is approximately 60% in MIBC [3,4].

Objectives

Methods

Results