癌症科学与治疗

Background: It is well known that Newcastle Disease Virus (NDV) AF2240 has antitumor activity against breast cancer cell lines. Several studies have thought this activity depend on direct viral oncolysis, which may not be the only factor that play a role in the antitumor effect of the virus. However, the mechanism underlying its antitumor effect is largely unresolved. In line with this observation, we postulated that NDV AF2240 may induce an in vitro production of Nitric Oxide (NO) and Tumor Necrosis Factor (TNF-α) in RAW 264.7 macrophages for cytotoxic activity on breast cancer cells.

Methods: NDV AF2240 were subjected to different experimental conditions (Live, UV-inactivated and Heatinactivated), different Heamagglutination (HA) titer of the virus were co-cultured with RAW 264.7 cells to get the cell-free supernatant. Levels of TNF-α, and NO production were measured by ELISA and Griess assay respectively. MTT assay was later used to determine their cytotoxicity on MDA-MB-231 breast cancer cell line in vitro.

Results: NDV was found to be an excellent inducer in RAW 264.7 macrophage cells of TNF-α (P<0.05) and NO production (P<0.05) when compared with the negative control. The supernatant containing NO and TNF-α was also found to be cytotoxic against MDA-MB-231 cells (P<0.05) when compared with the negative control, indicating that viral replication was not necessary for their production, because UV-inactivated NDV for 15 minutes was almost as good as lived NDV. However, heat inactivated NDV did not induce TNF-α and NO production.

Conclusion: This suggests the relevance of TNF-α and NO in the indirect antitumor effect of NDV AF2240, and also shown that mare contact between the macrophages and the NDV is enough to induce TNF-α and NO production in macrophages.

??????? 2 (COX-2) ??????????????????????????????????? COX-2 ???????????????????-???? (EMT)??????????????????? EMT ?????????????????IL-27 ????????????????????? IL-27 ?? STAT1 ?????? EMT?

??:?????????????IL-27??STAT????EMT??????????

?????? Western blot ?????IL-27 ?????????? (NSCLC) ?????? STAT1 ? STAT3 ???Snail ????????? (N-cadherin ? vimentin) ?????????? (E-cadherin?β- ? γ-catenins) ?????????????????? IL-27 ????? STAT1 ????????????????? IL-27 ??? STAT3 ????? STAT1 siRNA ?? STAT1 ??? IL-27 ???????????? EMT ?????????????? STAT1 siRNA ???????? IL-27 ???????? STAT1 ? STAT3 ????????????????????????????????????????????STAT1 siRNA?????STAT1??????????????????

????????IL-27?????????STAT1???????????????????????

????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????? (VEGF)?????????? (PDGF)?????????? (FGF) ?????? (Ang)/Tie 2 ????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????

???????????????????????????????????????????????????????????? FGFR2 ? TGFB1 ???????????????????????????????????????????????????? 100 ????????????? FGFR2 rs1219648 ? rs2981582 ? TC ???????????????? TGFB1 rs1800470 ? TC ??????????????????????????????? Mianwali ? Khushab ?????? Awan ? Rajput ???????????????????????????????????? 88 ?? T ???????????????????????????? C ??????????????????? FGFR2 ????????????????????????????????????????? TGFB1 ??? TGFB1 ????????????????????????????????????????????????????????????????????????????????????????????????40 ???????????????? 30 ????????????????P ??? 0.1?????????????????????????????????????????????? FGFR2 ????????????????????????? TGFB1 ???????????????????????????????????????????????

???????????? (HNC) ?????????????????????????????????????????? 40%??????????? HNC ?????????????/?????????????????????????? 11%???????????????????????????????????????????????

????? HNSCC ?????????????????????????????????????????????????????????????????????????????????????????????????????????????????? HNC ???????????

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????????????? DNA ???????????????? DNA ?????????????????RuvB-like (RUVBL) 2 ? TIP60 ? INO80 ??????????????????????????? DNA ??????????????? RUVBL2 ??????????????????

?????????? (si) RNA ???? MRC5-SV ???? RUVBL2????????????????? (cisPt)?2'-??-5-???? (azadC) ????? C (MMC)????? DNA ?????? X ????????

??????? 3 ??10 nM siRUVBL2 ?????? 80%?? 6 ??? (>65%) ?????????? siRNA ?????????? RUVBL2 ??????????????? RUVBL2 ??????????RUVBL2 ?????? cisPt?azadC ? X ??????????? MMC ???????????

?????? RUVBL2 ?????????? X ??????????????????????? X ?????????? DNA ????????????????????????????? RUVBL2 ???????????

???????? (MDR) ????????????????HIV ???????????????????????? (HAART) ???????? HIV ??????????????????????????????????????????????????????????????????????????????????????????????????

????????????????????? 72 ??????????? (LS180) ?????????????????????????? Vivid™ ?????????? (T47D) ??????? (PC-3) ?????????????????

???????????????????????????????????[3H]???????VIVID™??????????????????????????????????????????????????????????T47D?PC-3???????????????????????????????????

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