Gastric Cancer Cell Line HGC-27 Research Articles

Changes in gene expression profiles induced by parvovirus H‐1 in human gastric cancer cells

The autonomous parvovirus H-1 exhibits preferential toxicity for transformed or tumor cells. The precise molecular mechanism of H-1 virus-associated cytotoxicity is not fully understood. The present study aimed at gaining more information about parvovirus-induced cellular disturbances. The H-1 virus-sensitive human gastric cancer cell line HGC27 was analyzed in the present study. cDNA microarrays were used to determine the global cellular gene expression changes which occur during the process of H-1 virus-induced death of HGC27 cells. A subset of differential expressed genes was further tested by RT-PCR and Northern blot analyzes. A total of 920 genes belonging to various functional groups were found to be differentially expressed in H-1 virus- versus mock-infected cells in cDNA microarrays. Among them, 363 genes were upregulated, whilst 557 genes were downregulated. The differential expressions of some of these genes were further confirmed by RT-PCR and Northern blot analysis. Some of genes known to be involved in cell signal transduction, apoptosis, DNA replication, DNA repair, DNA binding and transcription were differentially expressed after parvovirus H-1 infection, they might play a role in H-1 virus-induced gastric cancer cell death. These genes represent interesting candidates to be tested at the functional level for their contribution to the disturbances triggered by H-1 virus in tumor cells.

Cardiovascular toxicity with cancer chemotherapy

Parameritannin A-2 (PA-2) is a natural product extracted from the stems of the plant Urceola huaitingii. Our previous studies have shown that PA-2 exhibits significant synergistic anticancer effects with doxorubicin (DOX) in HGC27 gastric cancer cell lines. Here we report that our isobolographic analysis confirms the synergistic cytotoxic effects of PA-2 and DOX in HGC27 cells. Flow cytometry and immunoblotting indicate that PA-2 enhances DOX-mediated apoptosis. Importantly, PA-2 enhances the intracellular accumulation of DOX in HGC27 cells. The combination of DOX and PA-2 remarkably increases the release of cytochrome C and the activation of caspase-3 and caspase-9, compared with DOX treatment alone. Moreover, PA-2 attenuates the DOX-induced activation of Akt, ERK1/2 and p38 signaling pathways, providing a molecular mechanism for the synergistic effects of DOX and PA-2 in the induction of apoptosis. In conclusion, our studies demonstrate that PA-2 and DOX synergistically induce mitochondria-dependent apoptosis as PA-2 inhibits the PI3K/Akt, ERK1/2 and p38 pathways in HGC27 cells. These findings suggest that the combination treatment with PA-2 and DOX may represent a potent therapy for gastric cancer.