Objective To investigate the role and molecular mechanism of galactose lectin-1（Galectin-1, Gal-1） in the inhibition of cholangiocarcinoma cell proliferation by metformin. Methods HuCCT1 cells were treated with different doses of metformin for 24, 48 and 72 h. The effect of metformin on cell survival was detected by CCK8, and cells were treated with 0 and 20 mmol/L of metformin for 24 h. The effects of metformin on cell clone formation, cell cycle and apoptotic vesicles were analyzed by clone formation assay, flow cytometry and DAPI staining. The expression of Gal-1 in cholangiocarcinoma and its effect on the survival rate of cholangiocarcinoma patients were analyzed using TCGA, GEPIA, UALCAN, HPA and other databases;the expression changes of Gal-1 in intrahepatic cholangiocarcinoma tissues and paracancerous tissues were detected by immunohistochemistry; cells were treated with 0 and 20 mmol/L metformin for 24 h, and Gal-1 and the protein PI3K, which is closely related to cell proliferation, were detected using Western Blot. The cells were treated with 0 and 20 mmol/L metformin for 24h. The protein expression of Gal-1 and closely related proteins PI3K, AKT and mTOR were detected by Western Blot. Results The cell survival rate decreased significantly with the increase of metformin treatment concentration and treatment time, and the results of clone formation assay showed that the clone formation rates of control and 20 mmol/L metformin treated groups were 18.17% and 1.98%, respectively. The metformin treated groups showed significant G2 phase cell block and were accompanied by the formation of a large number of apoptotic vesicles. The results of biochemical analysis showed that Gal-1 expression was significantly increased in cholangiocarcinoma cells, and the results of immunohistochemistry using cancer and paraneoplastic tissues were consistent with the results of biochemical analysis, and the high expression of Gal-1 was closely associated with OS in cholangiocarcinoma patients; the expression of Gal-1 was significantly decreased in metformin-treated HuCCT1 cells, and accompanied by the inhibition of PI3K/AKT signaling pathway; in addition, inhibition of Gal-1 expression not only reduced cell proliferation ability but also restricted the inhibition of PI3K/AKT signaling pathway. Conclusion Metformin can inhibit the activation of PI3K/AKT signaling pathway by suppressing Gal-1 expression in intrahepatic cholangiocarcinoma, which in turn leads to the inhibition of cell proliferation.

根据WHO分类,印戒细胞癌(signet ring cell carcinoma,SRCC)是一种特殊类型的黏液分泌型腺癌,多见于消化系统,最常见的部位是胃(86.8％)、结直肠(3.6％)和胆囊(2.5％),偶发于乳腺、膀胱、前列腺和肺[1],而原发于壶腹部的印戒细胞癌罕见[2].现报道2021年12月湖南师范大学附属第一医院肝胆外科收治的1例壶腹部腺癌伴印戒细胞癌,总结壶腹部腺癌伴印戒细胞癌的临床特点、治疗及预后,提高对该病的临床诊治水平.

患者女，66岁，2023年1月29日因“下腹部不适”于湖南省人民医院肝胆外科治疗。入院查体：患者一般情况可，子宫右侧可扪及一个囊性包块，大小约为13 cm×12 cm×12 cm，无压痛，边界清，活动度差。辅助检查：糖类抗原199为489.36 U/mL，糖类抗原125为158.75 U/mL，其他肿瘤标志物正常。胸部+上腹部+下腹部+盆腔横断面CT增强扫描：（1）胆囊颈部及胆囊管占位，性质待定，考虑肿瘤可能；胆囊结石伴胆囊炎。（2）盆腔巨大囊实性占位。（3）宫颈占位性改变，考虑宫颈肿瘤（图1A）。2023年2月5日宫颈活检结果：宫颈管高级别鳞状上皮内瘤变，尚不能排除卵巢和子宫肿瘤为胆囊肿瘤转移的可能性。遵循患者及患者家属强烈的手术意愿，于2023年2月24日实施胆囊癌根治+盆腔肿物切除+子宫切除+肠部分切除手术。