Wang Wen-Jia, Qin Si-Hao, Zhang Ji-Wei, Jiang Yue-Yao, Zhang Jin-Nan, Zhao Lei
Institute of Pharmacy, Jilin University, Changchun, Jilin, China E-mail :
Asian Pac J Cancer Prev. 2014;15(22):9667-72. doi: 10.7314/apjcp.2014.15.22.9667.
Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-α (IFN-α) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms.
A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-α (IFN-α) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-α (IFN-α) on the ligands of NK and T cells was assessed by flow cytometry.
The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-α (IFN-α) may be a potential strategy for treating pancreatic adenocarcinoma.
胰腺腺癌是一种具有显著发病率和死亡率的恶性胃肠道癌症。尽管化疗有严重的副作用，但免疫疗法联合化疗已成为一种常见的临床治疗方法。在本研究中，我们调查了阿霉素与干扰素-α（IFN-α）联合治疗对小鼠胰腺癌Panc02细胞的体内外疗效及潜在机制。
建立荷Panc02小鼠模型，以确定阿霉素和干扰素-α（IFN-α）是否能有效抑制体内肿瘤生长。使用标准乳酸脱氢酶释放试验评估自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）的细胞毒性。为了评估NK细胞和CD8 T细胞与联合治疗介导的抗肿瘤作用的相关性，分别通过注射抗去唾液酸GM-1抗体或抗CD8抗体在荷瘤小鼠中使其耗竭。最后，通过流式细胞术评估阿霉素+干扰素-α（IFN-α）对NK和T细胞配体的影响。
联合治疗组在体内对Panc02的生长有显著抑制作用，这是由NK细胞和CTL的活化细胞毒性所致。耗竭CD8 T细胞或NK细胞可降低免疫化疗介导的抗癌作用。此外，阿霉素+IFN-α治疗增加了Panc02细胞上主要组织相容性复合体I类（MHC I）和NKG2D配体的表达，表明联合治疗可能是增强肿瘤免疫原性的潜在策略。所有这些数据表明，使用阿霉素和干扰素-α（IFN-α）的联合治疗可能是治疗胰腺腺癌的潜在策略。
