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血小板集聚过程依赖Ca~(2+)参与,而血小板集聚在肿瘤转移中起重要作用。戊脉安(Verapamil)能改变细胞Ca~(2+)环境,有证据表明它可减慢某些抗癌药的细胞外排、降低抗药性,具有抗癌协同作用。鉴此,作者观察戊脉安对肿瘤转移的影响,并初步探讨其作用机制。评价戊脉安抗转移作用分4方面进行:(1)雄性C57BL/6J 小鼠静注接种B16BL-6细胞,接种前2天开始腹腔内给药30~50mg/kg连续6天。接种后25天计数肺转移结节,有50~70%抑制率;(2)小鼠右前脚掌皮下接种B16BL-6细胞,接种后5天开始腹腔内给药,共给11天,在第17天切除带瘤肢,38天时观察淋巴结和肺转移情况。结果显示戊脉安不能抑制腋下淋巴结转移,但对肺转移约有25~80%抑制作用,在第17天测量带瘤脚掌厚度,也有轻度减少;(3)雄性BALB/c 小鼠静注接种C26NL-17细胞,腹腔内给药自接种前2天开始,共给6天,在23天观察到肺转移抑制约80%;(4)小鼠右前脚掌皮下接种C26NL-22细胞,接种第6天开始腹腔内给药共7天,第13天切除带瘤右前肢,在第29天观察到对肺转移50~60%抑制作用。对原位肿瘤也轻度抑制。同时,作者研究戊脉安对三种瘤细胞诱导对应动物血小板集聚的影响。取0.2ml 含血小板血浆(1~3.5×
Platelet aggregation depends on Ca 2+ participation, and platelet aggregation plays an important role in tumor metastasis. Verapamil can change the Ca 2+ environment of cells, and there is evidence that it can slow the extracellular efflux of certain anticancer drugs, reduce drug resistance and have anti-cancer synergism. In view of this, the author observed the verapamil on tumor metastasis, and preliminary study of its mechanism of action. Evaluation of verapamil anti-metastasis in four aspects: (1) Male C57BL / 6J mice were inoculated with B16BL-6 cells, 2 days before inoculation began intraperitoneal administration of 30 ~ 50mg / kg for 6 consecutive days. (2) B16BL-6 cells were inoculated subcutaneously in the right forelegs of the mice and were administered intraperitoneally 5 days after inoculation for a total of 11 days. On the 17th day after inoculation, Day excision with tumor limbs, 38 days observed lymph node and lung metastases. The results showed that verapamil can not inhibit the axillary lymph node metastasis, but about 25 ~ 80% inhibition of lung metastasis, measured on the 17th day the thickness of the tumor footpad, but also mildly reduced; (3) male BALB / c mouse static C26NL-17 cells were seeded intraperitoneally for 6 days starting from 2 days prior to inoculation, and about 80% of lung metastasis was observed on day 23. (4) C26NL-22 cells were inoculated subcutaneously in right anterior palms of mice and inoculated Intraperitoneal administration was started on day 6 for a total of 7 days, the right forelimb was excised on day 13, and the inhibition of lung metastases by 50-60% on day 29 was observed. Mild tumor suppression in situ. At the same time, the author studied the effects of verapamil on platelet aggregation induced by three kinds of tumor cells. Take 0.2ml platelet-containing plasma (1 ~ 3.5 ×