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目的:探讨三氧化二砷(As2O3)对人卵巢癌顺铂耐药细胞株3AO/DDP细胞裸鼠腹腔移植瘤的影响及其作用机制。方法:4×106个3AO/DDP细胞接种于裸鼠腹腔96 h后,随机分为5组,分别腹腔内注射0.2 mL生理盐水、3 mg/kg的DDP及0.8、1.2和2.4 mg/kg的As2O3,观察3AO/DDP细胞在各组裸鼠的致瘤率、裸鼠的死亡率及生存期;采用RT-PCR技术观察As2O3作用停药后1 d、1周、2周裸鼠腹腔移植瘤Fas、N-myc、nm23 H1及MTA1基因表达的变化,并与对照组相比较。结果:As2O3组裸鼠的致瘤率分别为87.5%、62.5%和50.0%,死亡率分别为62.5%、12.5%和0,生存期分别为(75.88±14.21)、(88.88±3.18)和(90.00±0.00)d,与DDP组的100%(致瘤率)、100%(死亡率)、(28.25±2.25)d(生存期)相比,差异有统计学意义,P<0.05;As2O3作用后,裸鼠腹腔移植瘤Fas及nm23 H1基因的表达水平升高,于停药第2周达到高峰,分别与对照组相比,差异均有统计学意义,P值均<0.05;N-myc和MTA1基因的表达在停药第1天和第1周下降,与对照组相比,差异有统计学意义(P<0.05),而第2周反弹升高,与对照组相比,差异无统计学意义,P>0.05。结论:As2O3对人卵巢癌裸鼠腹腔移植瘤具有明显的抑制作用,其机制与Fas和nm23 H1基因与N-myc和MTA1基因的正负调节有关。
Objective: To investigate the effect of arsenic trioxide (As2O3) on the transplanted abdominal tumor of human ovarian cancer cell line 3AO / DDP and its mechanism. Methods: 4 × 106 3AO / DDP cells were inoculated intraperitoneally into nude mice for 96 hours and were randomly divided into 5 groups. The mice were injected intraperitoneally with 0.2 mL saline, 3 mg / kg DDP and 0.8, 1.2 and 2.4 mg / kg As2O3 was used to observe the tumorigenicity rate of 3AO / DDP cells in nude mice and the mortality and survival rate of nude mice in each group. RT-PCR was used to observe the effect of As2O3 on the 1st, 2nd, Fas, N-myc, nm23 H1 and MTA1 gene expression changes compared with the control group. RESULTS: The tumorigenic rates of nude mice in As2O3 group were 87.5%, 62.5% and 50.0%, respectively. The mortality rates were 62.5%, 12.5% and 0 respectively. The survival rates were (75.88 ± 14.21), (88.88 ± 3.18) and 90.00 ± 0.00) d, compared with 100% (tumorigenicity), 100% (mortality), (28.25 ± 2.25) d (survival) in DDP group, the difference was statistically significant , The expression of Fas and nm23 H1 genes in peritoneal xenografts of nude mice increased and reached a peak at the second week after drug withdrawal. There were significant differences between the two groups (P <0.05), N-myc And the expression of MTA1 decreased on the first day and the first week of withdrawal, compared with the control group, the difference was statistically significant (P <0.05), while the second week rebound increased, compared with the control group, the difference was not Statistical significance, P> 0.05. Conclusion: As2O3 can significantly inhibit the transplanted human ovarian cancer in nude mice. The mechanism is related to the positive and negative regulation of Fas and nm23 H1 genes and N-myc and MTA1 genes.