Li Dan, Li Junmei, Yu Feng, Wang Bo, Liu Bing
School of Pharmacy, Qilu Medical University, Zibo, Shandong 255300, P.R. China.
Department of Pharmacy, Dezhou People's Hospital, Dezhou, Shandong 253000, P.R. China.
Oncol Lett. 2023 Apr 13;25(6):225. doi: 10.3892/ol.2023.13811. eCollection 2023 Jun.
Colon cancer is a digestive tract tumor with one of the highest frequencies worldwide, and with a high fatality rate. The present study aimed to investigate the expression and regulation of inflammatory factors in tumor tissues, monocytes and blood samples in patients with colon cancer (n=46) following treatment with neoadjuvant chemotherapy combined with tetrandrine. All patients underwent tumor resection after neoadjuvant chemotherapy. In the experimental group, 20 cases took tetrandrine during chemotherapy, while in the control group, 26 cases underwent chemotherapy without tetrandrine. Reverse transcription-quantitative PCR and western blotting were performed to detect the mRNA and protein expression levels of TNF-α. ELISA was used to detect the cytokine/chemokine expression levels [IL-15, IL-1β and IL-6, as well as chemokine ligand (CCL)2, CCL5, CCL20, chemokine (C-X-C motif) ligand CXCL1, CXCL2, CXCL3, CXCL5 and CXCL10 in the culture supernatant of colon cancer tissue]. Human blood mononuclear cells were cultured, and cytokine release was determined by ELISA. Cell proliferation ability was assessed using the MTT assay. Compared with the control group, the mRNA and protein expression levels of tumor necrosis factor-α (TNF-α) were downregulated in tumor tissues and serum and the serum levels of IL-15, IL-1β and IL-6 were relatively low in the experimental group. The expression levels of CCL5, CXCL2 and CXCL10 in the supernatant of cancer tissue culture were relatively low, compared with the conditioned medium prepared from tumor tissues of patients not receiving tetrandrine. When the cultured blood mononuclear cells were stimulated by the tissue culture supernatant from the experimental group, less IL-15, IL-1β and IL-6 were released, compared with the medium of tumor tissues of patients not taking tetrandrine. Following stimulation with the tissue culture supernatant from the experimental group, the proliferation ability of HCT116 colon cancer cells significantly declined. During chemotherapy of patients with colon cancer, tetrandrine may inhibit the expression of TNF-α in cancer tissues and blood, reduce the release of inflammatory factors and chemokines and decrease cancer cell proliferation. These findings provide a theoretical basis for the treatment of colon cancer in the clinic.
结肠癌是一种在全球发病率极高且致死率也很高的消化道肿瘤。本研究旨在调查新辅助化疗联合粉防己碱治疗后的结肠癌患者(n = 46)肿瘤组织、单核细胞及血液样本中炎症因子的表达及调控情况。所有患者在新辅助化疗后均接受了肿瘤切除术。实验组20例患者在化疗期间服用粉防己碱,而对照组26例患者仅接受不含粉防己碱的化疗。采用逆转录定量聚合酶链反应和蛋白质印迹法检测肿瘤坏死因子-α(TNF-α)的mRNA和蛋白表达水平。酶联免疫吸附测定法用于检测细胞因子/趋化因子的表达水平[白细胞介素-15(IL-15)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6),以及趋化因子配体(CCL)2、CCL5、CCL20、趋化因子(C-X-C基序)配体CXCL1、CXCL2、CXCL3、CXCL5和CXCL10在结肠癌组织培养上清液中的水平]。培养人血单核细胞,并用酶联免疫吸附测定法测定细胞因子释放情况。采用MTT法评估细胞增殖能力。与对照组相比,实验组肿瘤组织和血清中肿瘤坏死因子-α(TNF-α)的mRNA和蛋白表达水平下调,且血清中IL-15、IL-1β和IL-6水平相对较低。与未接受粉防己碱治疗患者的肿瘤组织制备的条件培养基相比,癌组织培养上清液中CCL5、CXCL2和CXCL10的表达水平相对较低。当用实验组的组织培养上清液刺激培养的血单核细胞时,与未服用粉防己碱患者的肿瘤组织培养基相比,释放的IL-15、IL-1β和IL-6较少。用实验组的组织培养上清液刺激后,HCT116结肠癌细胞的增殖能力显著下降。在结肠癌患者化疗期间,粉防己碱可能抑制癌组织和血液中TNF-α的表达,减少炎症因子和趋化因子的释放,并降低癌细胞增殖。这些研究结果为临床治疗结肠癌提供了理论依据。