Endo K, Maehara Y, Ichiyoshi Y, Kusumoto T, Sakaguchi Y, Ohno S, Sugimachi K
Cancer Center of Kyushu University Hospital, Fukuoka, Japan.
Cancer. 1996 Apr 15;77(8 Suppl):1681-7. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1681::AID-CNCR39>3.0.CO;2-U.
We examined the relationship between the expression of a multi-drug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer.
In 75 patients with gastric cancer, the expression of MRP was immunohistochemically investigated and the expression of MRP mRNA was also detected using reverse transcription PCR (RT-PCR). Sensitivity to the anticancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl[2H]-tetra-zolium bromide} assay. The relation between MRP expression and development, invasion, and metastasis of cancer was analyzed, and overexpression of the tumor suppressor gene p53 was investigated, immunohistochemically.
Immunohistochemically detected MRP positive tumors were noted in 34 of 75 excised tumors (45%), and confirmed by RT-PCR. There was no significant relation between MRP expression and clinicopathologic features or prognosis. Positive p53 staining was evident in 16 of 34 MRP positive tumors (47%) and 18 of 41 negative ones (44%), and there was no significant correlation between MRP and abnormal p53 expression. The MTT assay showed that MRP positive gastric cancer tissue was less sensitive to CDDP, DXR, and MMC compared with MRP negative ones. A similar tendency was noted with VP-16.
MRP expression relates to the chemosensitivity of tumor cells against some anticancer drugs and is independent of known factors related to the development, invasion, and metastasis of human gastric cancers.
我们研究了多药耐药相关蛋白（MRP）的表达与人类胃癌侵袭和转移的生物学因素之间的关系。
对75例胃癌患者，采用免疫组织化学方法研究MRP的表达，并使用逆转录聚合酶链反应（RT-PCR）检测MRP mRNA的表达。采用MTT {3-(4,5-二甲基-2-噻唑基)-2,5-二苯基[2H]-四氮唑溴盐} 法检测对顺铂（CDDP）、阿霉素（DXR）、依托泊苷（VP-16）和丝裂霉素C（MMC）等抗癌药物的敏感性。分析MRP表达与癌症发生、侵袭和转移之间的关系，并采用免疫组织化学方法研究肿瘤抑制基因p53的过表达情况。
75例切除肿瘤中有34例（45%）经免疫组织化学检测发现MRP阳性肿瘤，并经RT-PCR证实。MRP表达与临床病理特征或预后之间无显著关系。34例MRP阳性肿瘤中有16例（47%）p53染色呈阳性，41例阴性肿瘤中有18例（44%）呈阳性，MRP与p53异常表达之间无显著相关性。MTT法显示，与MRP阴性的胃癌组织相比，MRP阳性的胃癌组织对CDDP、DXR和MMC的敏感性较低。VP-16也有类似趋势。
MRP表达与肿瘤细胞对某些抗癌药物的化疗敏感性有关，且独立于与人类胃癌发生、侵袭和转移相关的已知因素。
