重组人催乳素(rhPRL)在huPBL/SCID嵌合模型中对人直肠癌的治疗效应及免疫机理初探

Antitumor Effects of Recombinant Human Prolactin on Human Adenocar-cinoma-Bearing huPBL/SCID Mice and Its Immunological Mechanism

通过体内实验进一步证实rhPRL对机体免疫功能的调节作用,以及用于过继细胞免疫治疗的可能性。我们选用CB17 SCID纯系小鼠,腹腔注入人结肠腺癌细胞(HT29),2小时后腹腔注入尼龙毛纯化的人淋巴细胞(T/NK细胞),同时开始进行rhPRL治疗,并设HBSS对照和rhIL-2治疗对照组。结果表明,rhPRL在体内外均无直接抗癌效应,反而可促进肿瘤生长。当SCID荷瘤鼠同时移植入人的T/NK细胞时出rhPRL可明显提高T/NK细胞的抗癌效果,生存期明显延长(P<0.05)。平均生存期由70.4天延至112.1天,在对照组全部死亡时(d105),rhPRL治疗组有60％存活,且在实验终止时(>160天)仍有40％存活。分析其抗癌机理发现,rhPRL体外可直接促进人T/NK细胞增殖,其分泌上清可抑制肿瘤生长,同时发现人T/NK细胞与HT29共育4小时中rhPRL亦可直接促进杀伤活性。

In order to demonstrate the immune regulatory function of human prolactin and its potential in adoptive im-munotherapy, CB17 SCID mice were loaded with human colon adenocarcinoma (HT29) i.p. and then injected i.p. with nylon wool purified human T and NK cells from PBL, followed by rhPRL treatment. The results showed that rhPRL did not exert direct inhibitory ffects on HT-29 cell, in contrast to it, improved the tumor cell growth both in vitro and in vivo . After SCID mice reconstituted with human T and NK cells, rhPRL increased the antitumor effects of human T and NK cells in HT-29-bearing SCID mice, demonstrating the prolonged survival period from 70.4 days to 112.1 days, and the increased survival rate from all died to 60% survival at day 105 compared with HBSS group. In vitro experiments, it was found that rhPRL might improve the proliferation of human T and NK cells, the supernatant of which may inhibit the growth of HT-29 cells in vitro, and improve the cytotoxicity of human T and NK cells against HT-29 tumor cells in 4-hour coculture.