消化道肿瘤转移淋巴结中P糖蛋白和谷胱甘肽S转移酶π的表达与肿瘤化疗药物敏感性的关系

Relationship between expression of P-glycoprotein, GST-xr and chemosensitivities in lymph node metastases of gastrointestinal carcinomas

目的探讨消化道肿瘤淋巴结转移灶中P糖蛋白（P-gp）和谷胱甘肽S转移酶π（GST-π）的表达与化疗药物敏感性的关系及其临床意义。方法对54例胃癌和大肠癌新鲜肿瘤组织及转移淋巴结进行肿瘤细胞培养化疗药敏性实验，行原发灶和转移灶P-gP和GST-π免疫组化染色。结果①肿瘤原发灶和淋巴结转移灶中P-gp和GST-π表达一致率较低，分别为22％（k=-0．0133，P=0．8698）和50％（k=0．1137，P：0．1496）；淋巴结转移灶中P-gp和GST-π表达强度均明显高于原发灶（Z=-3．0448，P=0．0023；Z=-2．1178，P=0．0034）。②VCR、OPT、OXA、DDP、MTX对淋巴结转移灶肿瘤细胞抑制率明显低于原发灶（均P〈0．05），仅VP-16对原发灶的抑制率明显低于转移灶（P=0．0406）。③原发灶中P．gP表达程度与5-FU、VCR和PTX对肿瘤细胞抑制率呈负相关（r=-0．4142～-0．5712，均P〈0．05），GST-π表达程度与5-FU、VCR、OPT和PTX的抑制率呈负相关（r=-0．3927～-0．4951，均P〈0．05）；转移灶中P-gP表达程度与VP-16、PTX和eADM对肿瘤细胞抑制率呈负相关（r=-0．3802～-0．4624，均P〈0．05），GST-π表达程度与5-FU、VCR、DDP的抑制率呈负相关（r=-0．3996--0．5345，均P〈0．05）。结论消化道肿瘤淋巴结转移灶中P-gp和GST-π的表达以及对化疗药物的敏感性均存在与原发灶不同的异质性，淋巴结转移灶具有更强的耐药倾向。术后辅助化疗的靶目标应针对淋巴结转移灶。

Objective To investigate the relationship between expression of P-glycoprotein （P-gp）, glutathione S-transferase-π （GST-π） and chemosensitivities in lymph node metastases （LNMs） of gastrointestinal carcinomas. Methods Tumor ehemosesitivities to 9 drugs was measured by MTT assay, and the expression of P-gp and GST-π were determined immunohistochemically in primary tumor （PT） and LNMs of gastrointestinal carcinomas in 54 patients. Results The P-gp expression was detected in 22% cases （k= -0.0133, P =0.8698） for both PT and LNMs, and of GST-π in 50% （k =0. 1137, P= 0. 1496）. Expression of P-gp and GST-π in LNMs were stronger compared with PT （Z = -3. 0448, Z = -2. 1178, both P 〈0. 05）. The inhibition rates of LNMs cells for VCR, OFF, OXA, DDP and MTX were lower than those to PT （ all P 〈 0. 05 ） , but for VP-16 it was higher （P 〈 0.05 ）. In PT, there were negative correlation between expression of P-gp and inhibition rates of tumor cells for 5-FU, VCR and PTX respectively （r = -0. 4142 - -0. 5712, all P 〈0. 05） , and GST-π for 5-FU, VCR, OPT and PTX as well （r = -0. 3927- -0. 4951, all P 〈0. 05）. In LNMs, negative correlation between expression of P-gp and inhibition rates of tumor cells for VP-16, PTX and cADM were found statistically （ r = - 0. 3802 - - 0. 4624, all P 〈 0. 05 ） , and also GST-π for 5-FU, VCR and DDP （ r = - 0. 3996 - - 0. 5345, all P 〈 0. 05）. Conclusions The LNMs of gastrointestinal carcinomas are heterogeneous with respect to chemotherapy, and more resistant than the PT for chemotherapeutants. Effective adjuvant chemotherapy in gastrointestinal cancers depends on targeting the metastatic component of the tumor.