Effects Of Aspirin Combined With Trastuzumab On Proliferation Of Ovarian Cancer SKOV3 Cells

Objective: To explore the effects of aspirin combined with trastuzumab on HER2 positive ovarian cancer SKOV3 cell lines,and to provide an experimental basis for targeted therapy of ovarian cancer.Methods: In this experiment human ovarian cancer SKOV3 cell lines were cultured in vitro with Mc Coy’s 5A culture medium for 24 h,48h,72 h,and 96 h.The experiment was divided into four groups: control group,aspirin group(1mmol/L,3mmol/L,6mmol/L),trastuzumab group(0.1μg/ml,1μg/m,10μg/ml,100μg/ml),and the combined group(aspirin3mmol/L + trastuzumab 10μg/ml),MTT assay was used to determine the effects of drugs on cell proliferative inhibition and the inhibition rate of drugs on cell proliferation was analyzed;the morphological changes and growth pattern of the drug-treated SKOV3 cells were observed under an inverted microscope;the cell cycle was detected by flow cytometry tests.Results:(1)After used of different concentrations of trastuzumab(0.1μg/ml,1μg/m,10μg/ml,100μg/ml)and aspirin(1mmol/L,3mmol/L,6mmol/L)in SKOV3 cells for 24 hours,48 hours,72 hours and 96 hours respectively.The results showed that trastuzumab had a slight inhibitory effect on SKOV3 cell proliferation(P > 0.05).However,aspirin significantly inhibited the proliferation of SKOV3 cells with an increase in concentration and time(P <0.05).Compared with aspirin or trastuzumab alone,the combined drugs significantly inhibited the proliferation of SKOV3 cells with an increase of time(P < 0.05).(2)In the control group,SKOV3 cells grew well,tight cell connection,clear medium without turbidity,full cell shape,clear boundary,and good light transmittance.Compared with a control group,the number of living cells slightly decreased in the trastuzumab group and the cell morphology was long spindle.Compared with a control group,the number of living cells decreased in the aspirin group,the intercellular space gradually widened,and the number of floating cells increased.Compared with the control group or the single drug group,showed a significant decrease in living cells in the combined drug group,the cell adhesion ability decreased,poor light transmission.(3)The results of flow cytometry showed that: Compared with the control group,trastuzumab group had no significant effect in the G0/G1 phase of SKOV3 cells(P > 0.05),aspirin group decreased the proportion ratio of SKOV3 cells in the G0/G1 phase(P > 0.05).Compared with the control group,the S phase distribution ratio of SKOV3 cells decreased in the trastuzumab group(P > 0.05),the S phase distribution ratio of SKOV3 cells increased in the aspirin group(P < 0.05),while the G2/M phase distribution ratio of SKOV3 cells in trastuzumab group and aspirin group increased(P > 0.05).Compared with the control group,in the combined treatment group the distribution ratio of SKOV3 cells in the G0/G1 phase decreased(P < 0.05),while the distribution ratio of SKOV3 cells in the S phase and G2/M phase increased(P < 0.05).Conclusion:(1)The combination of aspirin and trastuzumab has a synergistic effect on the inhibition of ovarian cancer SKOV3 cells proliferation.(2)Aspirin combined with trastuzumab inhibit cell cycle distribution,resulting in G2/M phase arrest of HER2 positive ovarian cancer cells.