CO_2对卵巢癌移植瘤生物学行为及顺铂敏感性的影响

Effects of carbon dioxide on the biological behavior of ovarian carcinoma xenografts and xenograft sensitivity to cisplatin

目的探讨体外模拟的二氧化碳(CO2)气腹环境对人卵巢癌裸鼠皮下移植瘤生物学行为的影响,以及CO2气腹环境作用后该移植瘤对化疗药物敏感性的变化。方法将体外培养的人卵巢癌细胞(SKOV3)暴露于12mmHgCO2环境下分别持续1h(a组)、3h(b组),对照组(c组)细胞放入CO2培养箱中常规培养。将裸鼠配对后随机分为A、B、C3组(每组10对),分别于各组裸鼠左侧肩胛部皮下接种上述对应a～c组细胞悬液。明显成瘤后3d,将每组的10对裸鼠再随机分为:A1、B1、C1组(用药组),腹腔注射顺铂(DDP)5mg/kg,0.5mL,每周1次,共3周;A2、B2、C2组(非用药组),仅腹腔注射生理盐水0.5mL,每周1次,共3周。停药后次日脱臼处死全部裸鼠,测量肿瘤的体积和体质量,采用免疫组化法检测黏附分子CD44v6和抑癌基因nm23-H1在各组移植瘤中的表达。结果①CO2气体处理组的皮下移植瘤增殖速度快于对照组(P<0.01),CO2作用3h组快于1h组(P<0.01);②CO2处理组的移植瘤对DDP的敏感性较对照组降低(P<0.01);③各组间肿瘤组织的CD44v6和nm23-H1的表达差异无统计学意义(P>0.05)。结论①CO2气体对SKOV3细胞裸鼠皮下移植瘤的增殖有促进作用;②CO2环境作用后,移植瘤对DDP的敏感性下降;③CO2气体对肿瘤转移影响不大。

Objective To investigate the effects of carbon dioxide（CO2）pneumoperitoneum environment on the biological behavior and chemotherapy drug sensitivity of human ovarian carcinoma cell（SKOV3）xenografts in nude mice.Methods SKOV3 cells were exposed to a simulated laparoscopic CO2 pneumoperitoneum environment at 12 mmHg CO2 pressure for 1h（a group）or 3h（b group）.Cells in the control group（c group）were cultured in a standard CO2 incubator.The paired nude mice were randomly divided into the A,B,and C groups（n=10 pairs）.Cell suspensions were subcutaeously inoculated into the left scapular of nude mice in each group.After the tumors had apparently formed three days later,nude mice（10 pairs）were again randomly divided into two groups.A1,B1,and C1（DDP group）were intraperitoneally injected with cisplatin（5 mg/kg,0.5 mL,qw×3）;A2,B2,and C2（non-treatment groups）were intraperitoneally injected with saline（0.5 mL,qw×3）.All nude mice were sacrificed by dislocation on the day following drug withdrawal.Then tumor volume and weight were measured.Expressions of adhesion molecule（CD44v6）andnonmetastasis gene（nm23-H1）in xenograft tumors were analyzed by immunohistochemical staining.Results ①The proliferation rate of xenograft tumors in the CO2 treated groups was higher than that in the control group（P0.01）,and those treated for 3 hours was higher than for 1 hour（P0.01）.②Tumor sensitivity to DDP in the CO2 treated groups decreased compared with the control group（P0.01）.③There was no significant difference between the groups in expression of CD44v6 and nm23-H1（P0.05）.Conclusion Carbon dioxide promotes the proliferation of human ovarian carcinoma cell（SKOV3）xenografts in BALB/c nude mice,decreases tumor sensitivity to DDP and has no effects on tumor metastasis.