Adenovirus-mediated IL-24 expression enhances the chemosensitivity of multidrug-resistant gastric cancer cells to cisplatin

Abstract

Abstract. Chemotherapy is one of the commonly used strategies in gastric cancer, especially for unresectable patients, but it becomes insensitive to repeated administration of even the most effective chemotherapeutic agents, such as cisplatin. Given this, there is an urgent need for developing chemosensitizers to overcome acquired resistance to chemotherapeutic agents. Interleukin-24 (IL-24), a cytokine-tumor suppressor, shows broad-spectrum and tumor-specific antitumor properties, and studies have demonstrated that IL-24 could conspicuously restore the chemosensitivity of MDR cancer cells. Herein, we developed a human MDR gastric cancer cell subline, SGC7901/ CDDP, by repeated selection of resistant clones of parental sensitive cells, and further investigated the chemosensitizing effects and the underlying mechanisms of adenovirus-medi- IntroductionGastric cancer is the fourth leading cause of cancer-related death in the world (1). To date, chemotherapy is the most frequently used fundamental treatment for gastric cancer. However, the main barrier to successful chemotherapy is MDR caused by insensitivity to multiple chemotherapeutic agents after exposure to a single chemotherapeutic drug (2). For decades, the most representative consensus is the overexpression of drug efflux pumps (such as P-gp) occupying a critical position in development of MDR. Consequently, several innovative chemosensitizers against P-gp, such as verapamil, trifluoperazine and cyclosporine, have been found to enhance chemosensitivity of MDR phenotype cancer cells (3). However, the clinical application of these chemosensitizers showed disappointing results (4,5), indicating that there are some unknown molecules and mechanisms also responsible for MDR. Recent studies have verified that some novel factors including defective apoptosis pathway, enhanced DNA repair activity, or altered metabolism of drugs play a critical role in promoting formation of MDR (6). Though the underlying mechanisms have been deeply studied in vitro and in vivo (6-9), the precise mechanisms involved in MDR have not been Abbreviations: MDR, multidrug resistance; P-gp, P-glycoprotein;RT-PCR, reverse transcriptase polymerase chain reaction; IC 50 , 50% inhibitory concentration

Oncolytic adenovirus-mediated mda-7/IL-24 expression suppresses osteosarcoma growth and enhances sensitivity to doxorubicin

“…MDR compromises the efficacy of chemotherapy in clinical treatment, and therefore, eliminating MDR of cancer cells is urgently required for improving outcomes. IL-24 has been demonstrated to reverse the MDR phenotype of colon cancer (16), gastric carcinoma (17) and hepatoma (18), possibly by decreasing the expression of Pgp (16). Oncolytic adenovirus-mediated IL-24 expression also suppressed the resistance…”

CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest

“…EGF (epidermal growth factor) 17 , VEGF (vascular endothelial growth factor) 18 and HGF (hepatocyte growth factor) 19 have significant effects on oncogenesis, and they have been developed as targets for tumor therapy. On the other hand, some cytokines function as tumor suppressors, preventing and suppressing the development of cancer 20 , such as oncostatin M (OSM) 21 and interleukin-24 (IL-24) 22 . OSM is a multifunctional interleukin 6-related cytokine, which inhibits the proliferation of various solid tumor cell lines.…”

Role of Interleukins and New Perspectives in Mechanisms of Resistance to Chemotherapy in Gastric Cancer

“…In addition, Ad-IL-24 was related to up-regulation of Bax and down-regulation of p -gp and Bcl-2 in SGC7901/CDDP cells in vitro and in vivo. Consequently, these studies indicated that overexpression of the IL-24 gene can significantly promote chemosensitivity in GC cells with the MDR SGC7901/CDDP phenotype [ 45 ] ( Table 1 , Figure 1 ). These are the only studies on the role of IL-24 in the mechanisms of chemoresistance in GC.…”