Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs
Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs
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DOI：
10.1007/s00432-003-0492-0
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发表时间：
2003-12-01
影响因子：
3.6
通讯作者：
Sugihara, K
中科院分区：
文献类型：
--
作者：
Ohtsukasa, S;Okabe, S;Sugihara, K
目的。肿瘤特异性免疫治疗作为一种新兴的治疗晚期结直肠癌的方法具有很大的前景，并可能与标准化疗相结合，对肿瘤细胞产生协同抑制作用。为了研究免疫系统和化疗之间的相互关系，我们研究了肿瘤相关抗原CEA和抗原呈递系统的主要组成部分MHC-I类分子在多种化疗药物作用下的诱导。方法：研究方法。采用流式细胞术和半定量RT-PCR方法检测不同标准化疗药物对人结直肠癌细胞株MHC-I和CEA表达的影响。此外，还利用从注射的小鼠结肠癌细胞系衍生的荷瘤小鼠进行了研究，以确定持续向腹膜腔内注入化疗药物后MHC-I类分子的表达是否在体内发生变化，以及促进该因子的表达与治疗效果之间的相关性。结果。所有被检测的抗癌药物在IC50值给药时，都能诱导人类结肠癌细胞系COLO201中MHC-I类蛋白的表达。然而，只有在5-FU作用下才能诱导CEA mRNA的表达，而CDDP和SN-38处理后诱导的CEA mRNA表达不明显。联合应用5-FU和CDDP对COLO201细胞CEA的表达有额外的影响。在小鼠体内的研究中，只有在CDDP治疗的情况下，小鼠结肠癌细胞来源的肿瘤才会缩小，CDDP也介导了MHC I类分子的最高诱导。结论。这些结果表明，化疗药物会触发免疫系统，当与全身化疗联合使用时，癌症特异性免疫治疗可能会有效。
Purpose. Cancer-specific immunotherapy holds great promise as an emerging treatment for advanced colorectal cancer and may be combined with standard chemotherapy to provide a synergistic inhibitory action against tumor cells. To examine the interrelationship between the immune system and chemotherapy, we studied the induction of both CEA, a tumor-associated antigen, and MHC class I, a major component of the antigen presenting system, in response to a number of chemotherapeutic agents. Methods. The effect of a selection of standard chemotherapeutics on MHC class I and CEA expression in human colorectal cancer cell lines was determined by flow cytometry and semi-quantitative RT-PCR. In addition, studies using mice bearing tumors derived from an injected murine colon cancer cell line were performed to determine if alteration in MHC class I expression occurs in vivo following continuous infusion of chemotherapeutic agents into the peritoneal cavity, as well as to facilitate correlations between expression of this factor and therapeutic effectiveness. Results. All anti-cancer drugs examined, when given at IC50 values, induced expression of MHC class I protein in the human colon cancer cell line, COLO201. However, expression of CEA mRNA was only induced upon exposure to 5-FU, in contrast to obscure induction following CDDP and SN-38 treatment. Combined treatment with 5-FU and CDDP gave additional effect on CEA expression in COLO201 cells. Regarding the in vivo studies in mice, the size of the murine colon cancer cell-derived tumors was reduced only in response to treatment with CDDP, which also mediated the highest induction of MHC class I expression. Conclusion. These results suggest that chemotherapeutic agents trigger the immune system and cancer-specific immunotherapy may be effective when used in combination with systemic chemotherapy.