负载肿瘤细胞抗原的树突状细胞联合奥沙利铂抑制胰腺癌细胞BxPC-3增殖的实验研究

Effect of Oxaliplatin Plus Dendritic Cell Loaded Tumor Cell Antigen on Inhibiting Growth of Pancreatic Cancer BxPC-3 Cell

目的:化疗是晚期胰腺癌的主要治疗手段,但临床效果有限。为提高胰腺癌化疗效果,本研究将化疗药物奥沙利铂(OXA)联合肿瘤全细胞抗原负载的树突状细胞(DC)体外作用于胰腺癌BxPC-3细胞系,观察对其增殖的影响。方法:自健康人外周血中分离培养DC和T细胞。反复冻融BxPC-3细胞,使其裂解并提取全细胞抗原后致敏DC,再以DC激活T细胞。ELISA检测T细胞培养上清中IL-2、IL-4、IL-10和IFN-γ的含量。将T细胞与不同浓度的OXA联合作用于BxPC-3细胞,MTT法检测杀伤率。结果:负载BxPC-3全细胞抗原的DC能显著激活T细胞使其成为效应性T细胞,并使其分泌IL-2和IFN-γ。不同浓度的OXA与效应性T细胞联合作用于BxPC-3细胞可明显抑制其增殖,且杀伤效果与OXA的浓度呈正相关。结论:负载BxPC-3全细胞抗原的DC可诱导出抗肿瘤的效应性T细胞,联合OXA能显著提高对BxPC-3细胞的杀伤作用。生物治疗联合化疗抑制胰腺癌细胞增殖的作用明显,具有较好的临床应用前景。

Objective： Chemotherapy is the main treatment for advanced pancreatic cancer, but it＇s clinical effect is limited. To en- hance the effect of chemotherapy pancreatic cancer, in this study, oxaliplatin （OXA） and the dendritic cells （DCs） that was loaded BxPC-3 cells＇ whole antigen was jointly applied to BxPC-3 cell, and the effect on inhibiting proliferation of BxPC-3 cells was estimated. Methods： DCs and T lymphocytes were Isolated from blood of healthy adults and and cultured in vitro. Whole cell antigen of BxPC-3 cells were extracted with freeze thawing method and sensitized DCs. And then, T lymphocytes were activated by the DCs. The concentration of IL-2, IL-4, IL-10 and IFN-~ in culture supernatant ofT lymphocytes was measured by ELISA. Subsequently, the ability of different con- centration OXA combined with sensitized T cells to kill BxPC-3 cells were detected by MTT methods. Results： The whole cell antigen of BxPC-3 cells pulsed DCs could activated T cells and made them secrete IL-2 and IFN-y . Different concentration OXA plus activated T cells obviously inhibited the proliferation of BxPC-3 cells, and the killing effect was positively correlated with the concentration of OXA. Conclusion： DCs loaded BxPC-3 cells＇ whole antigen could induce anti-cancer cytotoxcity T cells and kill more tumor cells with OXA. This experimental evidence show that cancer biotherapy combining with chemotherapy could significantly inhibit proliferation of the pancreatic cancer cell, and this combination therapy has good prospects for cilinical appliation for pancreatic cancer treatment.