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[目的]建立单一剂量化疗药物治愈荷瘤小鼠的动物模型,为研究在体内化疗药物治愈肿瘤与机体免疫力和肿瘤细胞耐药之间的关系奠定基础。[方法]用MTT法在体外检测小鼠淋巴瘤EL4细胞对化疗药物美法仑的敏感性。野生型C57BL/6小鼠皮下接种小鼠淋巴瘤EL4细胞建立荷瘤小鼠模型,不同剂量的美法仑单次腹腔内注射,观察不同剂量的美法仑体内治疗的效果及其毒、副作用,找出美法仑可发挥最大抑瘤作用、并能使荷瘤小鼠的肿瘤消退、不再复发的最小治疗剂量。[结果]体外美法仑对EL4细胞的直接杀伤作用与所用美法仑的剂量呈正相关。接种1×105EL4细胞可使C57BL/6小鼠肿瘤进行性生长,接种后12 d平均肿瘤直径为6 mm,动物致死时间平均为(17.7±1.0)d。接种后12 d的荷瘤小鼠腹腔单次注射不同剂量的美法仑,观察发现:应用0.75 mg/kg~30 mg/kg的美法仑,肿瘤结节缩小的速率与所用美法仑的治疗剂量呈正相关;在肿瘤结节完全消退后,肿瘤的复发率与所用美法仑的治疗剂量呈负相关。7.5 mg/kg美法仑单次腹腔内注射后不但使野生型C57BL/6荷瘤小鼠的肿瘤完全消退,治疗后2个月内无肿瘤复发,并且再次接种等量肿瘤细胞无肿瘤生长。[结论]单一剂量(7.5 mg/kg)的美法仑腹腔内注射是可以治愈野生型C57BL/6荷瘤小鼠的最低有效剂量。该动物模型的建立为研究化疗药物治愈恶性肿瘤的机制奠定了基础。
[Objective] To establish animal model of single-dose chemotherapy for tumor-bearing mice and lay the foundation for the study of the relationship between chemotherapy-induced tumor in vivo and immunity and tumor cell resistance. [Method] The MTT assay was used to detect the chemosensitivity of melphalan to EL4 cells of mouse lymphoma in vitro. Wild type C57BL / 6 mice were subcutaneously inoculated with mouse lymphoma EL4 cells to establish a tumor-bearing mouse model. Different doses of melphalan were injected intraperitoneally to observe the effect and toxicity and side effects of different doses of melphalan in vivo , To find out the maximum inhibitory effect that melphalan can exert, and can make the tumor of tumor-bearing mice subside, no recurrence of the minimum therapeutic dose. [Result] The direct killing effect of melphalan on EL4 cells in vitro was positively correlated with the dose of melphalan. Inoculation of 1 × 105EL4 cells allowed the tumor to grow in C57BL / 6 mice. The average tumor diameter was 6 mm at 12 days after inoculation and the average lethal time of animals was (17.7 ± 1.0) days. A single injection of melphalan at different doses intraperitoneally on the 12th day after inoculation showed that the rate of tumor nodules shrinking was significantly lower than that of melphalan at 0.75 mg / kg to 30 mg / kg melphalan The treatment dose was positively correlated; after the tumor nodules completely regressed, the tumor recurrence rate was inversely related to the dose of melphalan used. After a single intraperitoneal injection of 7.5 mg / kg melphalan, the tumor of wild-type C57BL / 6 tumor-bearing mice completely disappeared. There was no tumor recurrence within 2 months after the treatment, and the same amount of tumor cells were seeded again without tumor growth. [Conclusion] The single dose (7.5 mg / kg) of melphalan intraperitoneal injection is the lowest effective dose to cure wild-type C57BL / 6 tumor-bearing mice. The establishment of this animal model lays the foundation for studying the mechanism of chemotherapy drugs in curing malignant tumors.