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Studies on the Mechanism and Reversing Drug Resistance of Soluble CD40 Ligand Treatment for Epithelial Ovarian Cancer in Vitro

Author: ZhangMinJie
Tutor: ZhangZhengMao；DanBaoEn
School: Hebei Medical University
Course: Obstetrics and Gynaecology
Keywords: sCD40L SKOV3 SKOV3/DDP Apoptosis Multidrug resistance
CLC: R737.31
Type: Master's thesis
Year: 2011
Downloads: 17
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Abstract


Purpose: One of the leading cause of death for ovarian cancer, gynecological malignancies, 5-year survival rate is still hovering around 30%. In recent years, the cytokine gene therapy has become a new type of cancer treatment, and more and more people's attention. CD40 is present in the immune cells, and a variety of tumor cells, tumor necrosis factor receptor superfamily member, has been demonstrated in the CD40 ligand CD40 positive induced apoptosis in human colon cancer, breast cancer and lung cancer cells. Soluble CD40 ligand (soluble CD40 ligand, sCD40L) The purpose of this study is to investigate the human epithelial ovarian cancer cell line SKOV3 and its proliferation of cisplatin-resistant ovarian cancer cell lines SKOV3/DDP possible mechanism provide a theoretical basis for sCD40L applied to the feasibility of treatment for ovarian cancer and ovarian cancer resistant to DDP. Method: a reverse transcription - polymerase chain reaction (RT-PCR) was used to detect the expression of the CD40 gene in SKOV3 and SKOV3/DDP cells. 2 Cell Titer 96 AQueous non-radioactive cell proliferation assay (MTS) to detect different concentration of sCD40L the proliferation of the SKOV3, SKOV3/DDP cells at different times, the simultaneous detection of different concentrations of cisplatin at the same time both cell proliferation . 3 MTS assay of sCD40L combined with cisplatin to inhibit the proliferation of of SKOV3, SKOV3/DDP cells. 4 flow cytometry sCD40L and sCD40L plus cisplatin treatment SKOV3 cells before and after the change of the cell cycle. 5 RT-PCR method to detect sCD40L and sCD40L plus cisplatin treatment SKOV3 cells before and after of survivin, caspase-3 and caspase-9 gene expression. 6 RT-PCR method to detect sCD40L and sCD40L combination with cisplatin MDR1, LRP, GST-π and survivin gene expression before and after treatment SKOV3 / DDP cells. Results: 1 of SKOV3 and SKOV3/DDP cells are CD40 expression, SKOV3 expression level was 0.281 ± 0.007, SKOV3/DDP expression levels with the concentration of 0.427 ± 0.012. 2 different concentrations of sCD40L inhibition of both cell increased with the increase were dose-dependent, the difference was significant (P lt; 0.05); same concentration acting on the two types of cells, inhibition differences significant sex (P gt; 0.05) between different concentrations. sCD40L SKOV3 cells 48h IC50 of 3.47μg/ml, the IC50 for 3.22μg/ml the SKOV3/DDP cells. 3 cisplatin IC50 of SKOV3/DDP cell 25.12μg/ml, SKOV3 cells (IC50 5.52μg/ml) 4.55 times that SKOV3/DDP cells resistant multiple of 4.55. 4 sCD40L plus cisplatin role in SKOV3 cells, cisplatin IC50 alone 5.52μg / ml, respectively, decreased to 2.61μg/ml and 1.46μg/ml. Of sCD40L1μg/ml combined with cisplatin role of after at SKOV3/DDP cells, so that the IC50 of cisplatin by single agent 25.12μg/ml decline 9.25μg/ml reversal fold 2.71; of sCD40L 2μg/ml plus cisplatin cisplatin The IC50 dropped to 4.83μg/ml, reversed a multiple of 5.20 of sCD40L role of cisplatin SKOV3/DDP cells after 48h of sCD40L group cisplatin sCD40L group appears increase in the proportion of G0/G1 phase, S phase decline in the proportion of drug concentration high, the more obvious the role of sCD40L in combination with cisplatin role is more obvious than when alone with sCD40L (P lt; 0.05). 6 SKOV3 cells were treated with sCD40L and cisplatin for 48h, each group of survivin mRNA expression level decreased gradually, caspase-3 mRNA and caspase-9 mRNA expression level was gradually increased, compared with the negative control group, the difference was statistically significant (P lt; 0.05). 7 SKOV3/DDP cells after each group of MDR1 mRNA, LRP mRNA, of GST-πmRNA and survivin mRNA expression level decreased gradually, sCD40L and cisplatin for 48h, compared with the negative control group, the difference was statistically significant (P lt ; 0.05). Conclusions: 1 of SKOV3 SKOV3/DDP cells are CD40 expression. 2 sCD40L can inhibit the proliferation of SKOV3 cells of sCD40L and cisplatin in combination can enhance the inhibitory effect of cisplatin on cell. sCD40L may cause cell cycle arrest in G0/G1 phase leaving the cell growth was inhibited, sCD40L may by down-regulating survivin gene, the increase of caspase-3, caspase-9 gene induced apoptosis of SKOV3 cells. The 3 sCD40L can inhibit the the cell proliferation SKOV3/DDP, and reversible SKOV3/DDP cells resistant to a certain extent. The sCD40L possibly through down of MDR1 of LRP, GST-π, survivin gene while reverse the SKOV3/DDP cells multidrug resistance.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Female genital tumors > Ovarian tumors
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