Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance

Background: The development of multidrug resistance (MDR) is a crucial problem of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Plasmacytoma variant translocation 1 (PVT-1), a long non-coding RNA (lncRNA), was previously found to be increased in gastric cancer patients and regulated the chemotherapy sensitivity in pancreatic cancer cells. However, the role of PVT1 in multidrug resistant Gastric cancer remains largely unexplored.

Methods: In this study, the mRNA levels of PVT1 in gastric cancer tissues of cisplatin-resistant patients and two kinds of cisplatin-resistant cells BGC823/DDP and SGC7901/DDP were detected by qRT-PCR. The influence of PVT1 knockdown or overexpression on anticancer drug resistance was assessed by measuring the cytotoxicity of cisplatin and the rate of apoptosis detected by CCK-8 assay and flow cytometry, respectively. Further, we investigated the expression levels of MDR1, MRP, mTOR and HIF-1α by qRT-PCR and western blotting.

Results: PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. In addition, BGC823/DDP and SGC7901/DDP cells transfected with PVT-1 siRNA and treated with cisplatin exhibited significant lower survival rate and high percentage of apoptotic tumor cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1α.

Conclusions: Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.