CIAPIN1 confers multidrug resistance by upregulating the expression of MDR-1 and MRP-1 in gastric cancer cells

Abstract

In a previous study, we observed that cytokine-induced apoptosis inhibitor 1 (CIAPIN1), a newly identified apoptosis inhibitor, was upregulated at the mRNA level in a multidrugresistant gastric cancer cell line SGC7901/VCR. The aim of this study was to explore the role of CIAPIN1 in the development of multidrug resistance (MDR) in gastric cancer cells. Upregulation of CIAPIN1 in MDR gastric cancer cells was confirmed by semiquantitative RT-PCR and Western blotting. Using cDNA transfection and RNA interference, we successfully established stable transfectants with upregulation (i.e., SGC7901-pCIAPIN1) or downregulation (i.e., SGC7901-pSiCIAPIN1 and SGC7901/ADR-pSiCIAPIN1) of CIAPIN1 expression, respectively. In vitro drug sensitivity assay demonstrated that overexpression of CIAPIN1 conferred MDR in SGC7901 cells whereas downregulation of CIAPIN1 sensitized SGC7901 and SGC7901/ADR cells to anticancer drugs. CIAPIN1 protected both SGC7901 and SGC7901/ADR cells from ADR-induced apoptosis and reduced intracellular accumulation and retention of adriamycin. Moreover, expression of P-glycoprotein (P-gp or MDR-1, a product of MDR-1 gene) and MDR-related protein-1 (MRP-1) was upregulated by CIAPIN1. In addition, Western blotting revealed that CIAPIN1 decreased the expression of Bcl-2, Bax and p53. Therefore, it is concluded that CIAPIN1 confers MDR in gastric cancer cells, likely by upregulating MDR-1 and MRP-1.

Changes in intracellular redox status influence multidrug resistance in gastric adenocarcinoma cells

“…These transporters mediate drug efflux from tumor cells and may further cause cross-resistance to multiple drugs with diverse chemical structures and curative efficacies. According to previous studies, MDR is observed in the majority of gastric cancers during treatment and is an significant cause of treatment failure (19,20,21).…”

“…The two main forms of MDR are intrinsic resistance, in which the previously untreated cancer cells are inherently insensitive to chemotherapeutic drugs, and acquired resistance, in which the cancer cells become insensitive as a result of chemotherapy (11,12). The most commonly reported mechanism for the acquisition of resistance to a broad range of anticancer drugs is the expression of one or more energy-dependent transporters, including P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), lung resistance protein (LRP) and breast cancer resistance protein (BCRP/MXR/ABCG2) (12)(13)(14)(15)(16)(17)(18)(19). These transporters mediate drug efflux from tumor cells and may further cause cross-resistance to multiple drugs with diverse chemical structures and curative efficacies.…”

Special AT-rich sequence binding protein 1 regulates the multidrug resistance and invasion of human gastric cancer cells

“…However, a significant percentage of gastric cancer patients fail to achieve complete remission, leading to a relapse or poor prognosis. Metastasis and multidrug resistance (MDR) have been regarded as major mechanisms underlying tumor relapse following successful surgical resections (1)(2)(3). Metastasis is the advanced stage of solid tumor progression and is a multi-step process that involves invasion, intravasation, extravasation to distant organs and finally growth of the secondary tumor.…”

Overexpression of CIAPIN1 inhibited pancreatic cancer cell proliferation and was associated with good prognosis in pancreatic cancer

“…4 In addition, our previous study confirmed that CIAPIN1 was upregulated in several multidrug resistance cancer cell lines and might have a role in mediating multidrug resistance of cancer cells. 5,6 Furthermore, CIAPIN1 expression was correlated with malignant phenotype of several cancers such as gastric cancer, liver cancer, esophagus cancer, lung cancer, lymphoma and kidney cancer, 7--15 which strongly suggested that CIAPIN1 might be an important protein involving in tumorigenicity and carcinogenesis.…”