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Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drugsensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

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The phosphoinositide 3-kinase pathway is one of the most commonly altered pathways in human cancers. The serum/glucocorticoid-regulated kinase (SGK) family of serine/threonine kinases consists of three isoforms, SGK1, SGK2, and SGK3. This family of kinases is highly homologous to the AKT kinase family, sharing similar upstream activators and downstream targets. Few studies have investigated the role of SGK2 in hepatocellular carcinoma. Here, we report that SGK2 expression levels were upregulated in hepatocellular carcinoma tissues and human hepatoma cell lines compared to the adjacent normal liver tissues and a normal hepatocyte line, respectively. We found that downregulated SGK2 inhibits cell migration and invasive potential of hepatocellular carcinoma cell lines (SMMC-7721 and Huh-7).We also found that downregulated SGK2 suppressed the expression level of unphosphorylated (activated) glycogen synthase kinase 3 beta. In addition, SGK2 downregulation decreased the dephosphorylation (activation) of β-catenin by preventing its proteasomal degradation in the hepatocellular carcinoma cell lines. These findings suggest that SGK2 promotes hepatocellular carcinoma progression and mediates glycogen synthase kinase 3 beta/β-catenin signaling in hepatocellular carcinoma cells.

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. Prostaglandin E2 (PGE2) regulates various biological processes, including invasion, proliferation and apoptosis. E-prostanoid 3 (Ep3) is a PGE2 receptor, and the functional role of Ep3 in the progression of NSCLC remains unresolved. The present study investigated the effects of Ep3 in A549 cells and explored the underlying molecular mechanisms. The results revealed that the mRNA and protein expression levels of Ep3 were significantly upregulated in NSCLC tissues and A549 cells. Pharmacological inhibition of Ep3 or RNA interference against Ep3 attenuated the cell viability, migration and invasion, and promoted apoptosis in A549 cells. Ep3 deficiency also decreased the expression of transforming growth factor (TGF)-β, phosphorylated (p)-Smad2 and p-Smad3. The transfection of TGF-β overexpression plasmids reversed the effects of Ep3 deficiency on the cell viability and apoptosis in A549 cells. Finally, an in vivo experiment revealed that Ep3-siRNA transfection strongly reduced the tumor growth and tumor volume. The Ep3-siRNA transfection also inhibited tumor metastasis via suppression of the expression of metastasis-associated proteins. Taken together, these findings indicate that inhibition of Ep3 attenuates the viability and migration, and promotes the apoptosis of NSCLC through suppression of the TGF-β/Smad signaling pathway. Targeting of the Ep3/TGF-β/Smad signaling pathway may be a novel therapeutic strategy for the prevention and treatment of NSCLC.