Abou-Shousha Seham A, Abdel-Mawla Ashour Abdel-Mawla A S, Hassan Safia M
Department of Immunology & Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Department of Histochemistry & Cell Biology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Egypt J Immunol. 2016 Jan;23(1):57-66.
It has been established that suppression of apoptosis during carcinogenesis is the main cause of development and progression of breast cancer. Breast cancer patients have higher circulating levels of IL-6 protecting cancer cells from apoptosis and positively correlated with poor prognosis of the disease. The current work is carried out to fulfill one of our in vivo preclinical studies' for approaching a novel breast cancer immunotherapy through induction of tumor cell apoptosis. The study aims at investigating the potential of anti-IL-6 monoclonal antibodies (mAbs) to suppress IL-6 anti-apoptotic activities in tumor microenvironment of malignant mammary tumor implanted-mice. To achieve this goal, 4 groups of mice were used, group I: served as control, group II: mice implanted with Ehrlich ascites carcinoma cell lines (EAC), through intramuscular injection till tumor inoculation, group III: injected intratumorally with10 µl saline for 3 successive days, and group IV: mice were injected intratumorally one day after tumor inoculation with a dose of 1.5 mg / kg of recombinent anti-IL-6 monoclonal antibodies in10 µl saline for 3 successive days. Apoptosis was evaluated in tumor samples from anti-IL-6 treated tumor implanted mice and compared with controls. Levels of apoptosis in tumor tissue samples of tumor implanted mice treated with anti-IL-6 were significantly (P=0.009) higher than untreated ones. In conclusion, anti-IL-6 monoclonal antibodies have the potential to suppress the anti-apoptotic effect of interleukin-6 (IL-6) within the tumor microenvironment of tumor implanted in mice.
现已证实，致癌过程中细胞凋亡的抑制是乳腺癌发生和发展的主要原因。乳腺癌患者循环中白细胞介素-6（IL-6）水平较高，该物质可保护癌细胞免于凋亡，且与疾病的不良预后呈正相关。当前的研究工作是为了完成我们的一项体内临床前研究，即通过诱导肿瘤细胞凋亡来探索一种新型的乳腺癌免疫疗法。该研究旨在调查抗IL-6单克隆抗体（mAbs）在植入恶性乳腺肿瘤的小鼠肿瘤微环境中抑制IL-6抗凋亡活性的潜力。为实现这一目标，使用了4组小鼠，第一组：作为对照组；第二组：通过肌肉注射接种艾氏腹水癌细胞系（EAC）直至肿瘤接种的小鼠；第三组：连续3天瘤内注射10 μl生理盐水；第四组：在肿瘤接种后一天开始，连续3天每天向小鼠瘤内注射1.5 mg/kg重组抗IL-6单克隆抗体（溶于10 μl生理盐水中）。对接受抗IL-6治疗的肿瘤植入小鼠的肿瘤样本进行凋亡评估，并与对照组进行比较。接受抗IL-6治疗的肿瘤植入小鼠肿瘤组织样本中的凋亡水平显著高于未治疗组（P=0.009）。总之，抗IL-6单克隆抗体有潜力在植入小鼠肿瘤的肿瘤微环境中抑制白细胞介素-6（IL-6）的抗凋亡作用。
