Role of p53β Isoform in Inhibitory Effect of rmhTNF Combined with Cisplatin on Human Gastric Cancer Cell Growth
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Graphical Abstract
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Abstract
Objective To investigate the biological function of p53β isoform, in the experiment that rmhTNF combined with cisplatin intervene in the growth of human gastric cancer cells MKN45 and SGC7901. Methods CCK-8 assay was applied to detect inhibition rates of gastric cancer cells MKN45 and SGC7901 interfered by different concentrations of rmhTNF alone or in combination with cisplatin. The change of p53βand bcl-2 mRNA expression were detected by Nested reverse transcription polymerase chain reaction(RTPCR). Results After different concentrations of rmhTNF alone or in combination with cisplatin(4μg/ml) intervened in MKN45 cells for 24h, the inhibition rate of combination group was higher than that of single group. The inhibition rate was increased with rmhTNF concentrations, with statistically significant difference between groups(P<0.05); in SGC7901 cells, the inhibition rate of combination group was increased but the difference was not statistically significant(P>0.05). rmhTNF alone had no effect on the expression of bcl-2 and p53β mRNA in MKN45 cells, and the difference was not statistically significant(F=0.006, P>0.05;F=1.179, P>0.05), but in combination with cisplatin could significantly upregulate p53β expression and downregulate bcl-2 expression and with the increasing concentrations of rmhTNF, p53β expression was gradually increased, bcl-2 expression was decreased, with statistically significant difference(F=18.577, P<0.01; F=169.309, P<0.01). The expression of p53β in SGC7901 cells was not observed, but blc-2 was over-expressed. When rmhTNF alone or in combination with cisplatin on SGC7901 cells, bcl-2 expression was reduced but the difference was not statistically significant(F=1.340, P>0.05). p53β and bcl-2 expression were negatively correlated(r=-0.897, P<0.01) and the inhibition rate was negatively correlated with bcl-2 expression(r=-0.906, P<0.01). Conclusion rmhTNF and cisplatin have significant inhibitory effect on p53β-positive gastric cancer cells MKN45. rmhTNF combined with cisplatin could exhibit synergistic antitumor which may be through p53β regulating its downstream molecules bcl-2 expression.
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