1.GOLPH3 regulates proliferation and apoptosis of endometrial carcinoma cells through PI3K/AKT/GSK3β signal
Chuncui LUO ; Chaoyan YUAN ; Qingfen CHEN
Journal of International Oncology 2020;47(2):65-69
Objective:To explore the mechanism of Golgi phosphoprotein 3 (GOLPH3) regulating the proliferation and apoptosis of endometrial cancer (EC) cells through PI3K/AKT/GSK3β signal.Methods:Human endometrial adenocarcinoma HEC-1-B cells were divided into control group, GOLPH3 group and GOLPH3 + GDC-0941 group. GOLPH3 was over-expressed by transfection of the GOLPH3 pcDNA. The PI3K inhibitor GDC-0941 was used to block the PI3K/AKT/GSK3β pathway. Cell viability, cell proliferation and apoptosis were measured by CCK-8 method, clone formation experiment and flow cytometry, respectively. The protein phosphorylation level in PI3K/AKT/GSK3β pathway was detected by Western blotting.Results:Transfection experiments were successful, and the PI3K inhibitor GDC-0941 did not affect GOLPH3 mRNA and protein expression. The relative cell viability of the control group, the GOLPH3 group and the GOLPH3 + GDC-0941 group were (100.00±4.63)%, (131.56±7.85)% and (97.85±7.36)%, and the difference among the three groups were significant ( F=7.437, P<0.001). The cell viability of the GOLPH3 group was higher than that of the control group ( P<0.001). The cell viability of the GOLPH3 + GDC-0941 group was lower than that of the GOLPH3 group ( P<0.001). The numbers of cell clones in the three groups were 46.86±3.56, 89.32±4.78 and 46.48±4.05, and the difference was significant ( F=20.437, P<0.001). GOLPH3 group had more clones than control group ( P<0.001). The number of clones formed in the GOLPH3 + GDC-0941 group was less than that in the GOLPH3 group ( P<0.001). The apoptosis rates of the three groups were (5.17±0.61)%, (2.34±0.56)% and (6.85±0.53)%, and the difference was significant ( F=11.643, P<0.001). The apoptosis rate of the GOLPH3 group was lower than that of the control group ( P<0.001), and the apoptosis rate of the GOLPH3 + GDC-0941 group was higher than that of the GOLPH3 group ( P<0.001). The phosphorylated PI3K/PI3K levels of the three groups were 1.00±0.09, 3.32±0.19 and 0.93±0.06, respectively; phosphorylated AKT/AKT levels were 1.00±0.11, 4.63±0.63 and 1.15±0.16, respectively; phosphorylated GSK3β/GSK3β levels were 1.00±0.08, 4.06±0.57 and 1.04±0.14, respectively. The differences were statistically significant ( F=12.532, P<0.001; F=16.792, P<0.001; F=15.311, P<0.001). The phosphorylation levels of each protein in the GOLPH3 group were higher than those in the control group (all P<0.001), and the GOLPH3 + GDC-0941 group were lower than the GOLPH3 group (all P<0.001). Conclusion:In EC cells, over-expression of GOLPH3 can promote cell proliferation and inhibit apoptosis by activating the PI3K/AKT/GSK3β pathway, suggesting that GOLPH3 is involved in the occurrence and development of EC.
2.Vector flow mapping technique for evaluating left ventricular diastolic function in ovarian cancer patients with postoperative chemotherapy
Chuncui CHEN ; Wenjuan QIN ; Ruimeng TIAN ; Ruoxi CHEN ; Yifei ZHOU ; Lei HUANG ; Xueting GUO ; Guilin LU
Chinese Journal of Interventional Imaging and Therapy 2024;21(8):477-481
Objective To observe the value of vector flow mapping(VFM)technique for assessing changes of left ventricular diastolic function in ovarian cancer(OC)patients who underwent postoperative chemotherapy.Methods Totally 37 OC patients who received postoperative chemotherapy were prospectively enrolled in chemotherapy group,while 40 healthy adults were taken as controls(control group).Routine echocardiography and VFM were performed for chemotherapy group before chemotherapy,after 3 and 6 cycles of chemotherapy,also for controls at enrollment,and comparison was performed between groups before chemotherapy,as well as among different time points within chemotherapy group,and the correlations of VFM results with hemoglobin and routine echocardiographic results in chemotherapy group were analyzed.Results No significant difference of age,body mass,body surface area(BSA),nor hemoglobin level,routine echocardiographic and VFM results before chemotherapy was found between groups(all P>0.05).With the process of chemotherapy,hemoglobin level gradually decreased,the isovolumic relaxation period(IR),atrial systole period(AS)intraventricular pressure difference(IVPD)and intraventricular pressure gradient(IVPG)of the left ventricle gradually increased(adjusted P<0.05),whereas routine echocardiography only showed that the left atrial volume index(LAVI)and the ratio of early mitral inflow velocity and the mean mitral annular early diastolic velocity(E/e')increased after 6 cycles of chemotherapy compared with those pre-chemotherapy(adjusted P<0.05).In chemotherapy group,VFM results in all diastolic subphases were strongly correlated with hemoglobin levels(|r|=0.718 to 0.836,all P<0.05),weakly to moderately correlated with LAVI(|r|=0.375 to 0.525,all P<0.05)and moderately correlated with E/e'(|r|=0.424 to 0.537,all P<0.05).Conclusion The diastolic function of left ventricle was probably damaged in early stage after postoperative chemotherapy in OC patients.VFM might detect slight changes of early diastolic function of left ventricle more sensitively than routine echocardiography.