Shanghai Pinghe School, Shanghai, 201206, China.
Stud Health Technol Inform. 2023 Nov 23;308:329-340. doi: 10.3233/SHTI230857.
Various damage-associated molecular patterns (DAMPs) associated with immunogenic cell death (ICD) have been discovered, potentially leading to cancer cell elimination. Certain platinum-based compounds can trigger both cancer cell apoptosis and ICD. This study aims to investigate the effect of the therapy of anti- PDL1 with Oxaliplatin by increasing amount and increasing treatment duration of anti-PDL1 with Oxaliplatin in SK-Br-3, both in vitro and in vivo conditions. The study will use HER-2 (3+) breast cancer cell line, SKBr3. The cells will be treated with increasing concentrations of Oxaliplatin with anti-PDL1 for different durations. In vitro death of cancer cells will be measured by MTT assay, HMGB1 will be measured by western blot. Additionally, ATP release will be measured, mice will be injected with SK-Br-3 and treated with the combo therapy of anti-PDL1 with Oxaliplatin, and in vivo tumor growth will be recorded weekly for xenograft. The positive control for the experiments is cisplatin, and the negative control is IgG solution instead of aPDL1 and Oxaliplatin in PBS.There are three main possible results: (1) The combo therapy of Oxaliplatin with anti-PDL1 induces robust ICD in HER-2 triple positive breast cancer cells. (2) The combo therapy of Oxaliplatin with anti-PDL1 act as a stimulant for robust ICD in HER-2(3+) positive breast cancer cells. (3) The combo-therapy of Oxaliplatin with anti-PDL1 has no significant effect on inducing robust ICD in HER-2(3+) positive breast cancer cells. The result of the study will provide important insight into the preclinical effectiveness of Oxaliplatin with anti-PDL1 in treating HER-2 (3+) breast cancer, and it also sets the basis for future clinical studies of the drug. Future studies should focus on investigating the mechanism underlying Oxaliplatin with anti-PDL1 effectiveness in SK-Br-3.
各种与免疫原性细胞死亡（ICD）相关的损伤相关分子模式（DAMPs）已被发现，这可能导致癌细胞消除。某些铂类化合物可以触发癌细胞凋亡和 ICD。本研究旨在探讨通过增加奥沙利铂联合抗 PD-L1 的剂量和延长奥沙利铂联合抗 PD-L1 的治疗时间，在体外和体内条件下对 SK-Br-3 进行抗 PD-L1 奥沙利铂治疗的效果。本研究将使用 HER-2（3+）乳腺癌细胞系 SKBr3。将细胞用不同浓度的奥沙利铂联合抗 PD-L1 处理不同时间。通过 MTT 测定法测量癌细胞体外死亡，通过 Western blot 测定 HMGB1。此外，还将测量 ATP 释放，将 SK-Br-3 注射到小鼠体内，并接受奥沙利铂联合抗 PD-L1 的联合治疗，并每周记录异种移植的体内肿瘤生长情况。实验的阳性对照为顺铂，阴性对照为 IgG 溶液代替 PBS 中的 aPDL1 和奥沙利铂。有三个主要的可能结果：（1）奥沙利铂联合抗 PD-L1 治疗可诱导 HER-2 三阳性乳腺癌细胞发生强烈的 ICD。（2）奥沙利铂联合抗 PD-L1 治疗可作为 HER-2（3+）阳性乳腺癌细胞发生强烈 ICD 的刺激物。（3）奥沙利铂联合抗 PD-L1 治疗对诱导 HER-2（3+）阳性乳腺癌细胞发生强烈 ICD 没有显著影响。该研究的结果将为奥沙利铂联合抗 PD-L1 治疗 HER-2（3+）乳腺癌的临床前疗效提供重要的见解，并为该药物的未来临床研究奠定基础。未来的研究应集中在探讨奥沙利铂联合抗 PD-L1 在 SK-Br-3 中有效性的机制。
