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奥沙利铂和英夫利昔单抗协同作用可诱导结肠癌消退。

Oxaliplatin and infliximab synergize to induce regression of colon cancer.

作者信息

Huang Di, Xue Jun, Li Shuguang, Yang Dongdong

机构信息

Department of Gastrointestinal Surgical Oncology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P.R. China.

Department of Vascular and Gland Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):1517-1522. doi: 10.3892/ol.2017.7468. Epub 2017 Nov 22.

Abstract

There is currently a lack of therapeutic options for patients with advanced colon cancer. Although certain chemotherapies are able to suppress the progression slightly, the response rate is low, and side effects of treatment and tumor recurrence continue to present problems for clinicians. Tumor necrosis factor-α (TNF-α) has been identified to possess tumor-promoting properties. In the present study, the effect of anti-TNF-α treatment (infliximab) in combination with chemotherapy on colon cancer was investigated. Tumor tissue samples were collected from patients with colon cancer who received oxaliplatin (OXA) treatment. Their TNF-α expression levels were examined with regard to their sensitivity to OXA. OXA-resistant colon cancer cell lines were established to explore the effects of anti-TNF-α treatment and OXA treatment. Furthermore, an OXA-resistant colon cancer xenograft mouse model was created and the effects of the combination treatment of anti-TNF-α and OXA on the mice were assessed. The results of the present study indicated that TNF-α was increased in the tumor tissue of patients with colon cancer who were resistant to OXA and also in OXA-resistant colon cancer cell lines. Anti-TNF-α treatment using infliximab inhibited the survival of OXA-resistant colon cancer cell lines by inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity effects. The combination of infliximab and OXA treatment achieved increased efficacy on the OXA-resistant colon cancer xenograft mouse model compared with treatment with OXA alone. On the basis of the results of the present study, it was concluded that infliximab may sensitize colon cancer cells to OXA treatment.

摘要

目前,晚期结肠癌患者缺乏治疗选择。尽管某些化疗方法能够略微抑制病情进展,但缓解率较低,而且治疗的副作用和肿瘤复发仍然给临床医生带来问题。肿瘤坏死因子-α(TNF-α)已被证实具有促肿瘤特性。在本研究中,研究了抗TNF-α治疗(英夫利昔单抗)联合化疗对结肠癌的影响。从接受奥沙利铂(OXA)治疗的结肠癌患者中收集肿瘤组织样本。检测其TNF-α表达水平及其对OXA的敏感性。建立奥沙利铂耐药的结肠癌细胞系,以探究抗TNF-α治疗和奥沙利铂治疗的效果。此外,构建了奥沙利铂耐药的结肠癌异种移植小鼠模型,并评估了抗TNF-α与奥沙利铂联合治疗对小鼠的影响。本研究结果表明,对奥沙利铂耐药的结肠癌患者的肿瘤组织以及奥沙利铂耐药的结肠癌细胞系中TNF-α水平均升高。使用英夫利昔单抗进行抗TNF-α治疗通过诱导抗体依赖性细胞毒性和补体依赖性细胞毒性作用,抑制了奥沙利铂耐药结肠癌细胞系的存活。与单独使用奥沙利铂治疗相比,英夫利昔单抗与奥沙利铂联合治疗在奥沙利铂耐药的结肠癌异种移植小鼠模型上取得了更高的疗效。基于本研究结果,得出结论:英夫利昔单抗可能使结肠癌细胞对奥沙利铂治疗敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0351/5774490/9459ec02369c/ol-15-02-1517-g00.jpg

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