肿瘤细胞治疗研究
英文原题：Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells.
Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells.
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新出现的证据表明，化疗药物和靶向抗癌药物对患者的健康细胞/组织具有严重副作用。为克服这一问题，将非肿瘤药物用作潜在癌症疗法的做法正日益受到关注。
在此，我们研究了一种名为meticrane的非肿瘤药物（一种用于治疗原发性高血压的噻嗪类利尿剂），据报道，该药物可显著提高抗CTLA4在AB1 HA肿瘤小鼠中的治疗效果。在我们假设驱动的研究中，我们测试了meticrane在血液系统恶性肿瘤（白血病和多发性骨髓瘤）和肝癌细胞系中的抗癌潜力。
我们的分析显示：1）Meticrane诱导了白血病细胞（Jurkat和K562细胞）和肝癌细胞（SK-hep-1）细胞活力和增殖的改变，然而，未检测到细胞凋亡的证据。2）Meticrane与表观遗传抑制剂（DNMT1/5AC、HDACs/CUDC-101和HDAC6/ACY1215）表现出相加/协同效应。3）全基因组转录分析显示，meticrane处理诱导了与非癌症相关通路相关的基因表达变化。
重要的是，差异表达基因与癌症基因组中的生存相关基因显示出良好的相关性。4）我们还进行了分子对接分析，发现meticrane对PD-L1、TIM-3、CD73和HDACs具有相当高的结合亲和力评分。
此外，我们测试了其用于癌症免疫治疗的适用性，但meticrane对细胞因子诱导的杀伤（CIK）细胞的细胞毒性未显示出反应。据我们所知，我们的研究是首次尝试识别并实验证实美替克仑的抗癌潜力，也是首次测试任何非肿瘤药物在 CIK 细胞治疗中的适用性。除此之外，我们还表达了在测试美替克仑过程中遇到的一些担忧，这些担忧在考虑用于未来临床或临床前目的时同样适用于其他非肿瘤药物。
综上所述，美替克仑参与了一些被动靶向癌细胞的抗癌通路，可能被认为与表观遗传抑制剂相容。
Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum.
Herein, we investigated one non-oncology drug named meticrane (a thiazide diuretic used to treat essential hypertension), which has been reported to indescribably improve the therapeutic efficacy of anti-CTLA4 in mice with AB1 HA tumors. In our hypothesis-driven study, we tested anti-cancer potential meticrane in hematological malignance (leukemia and multiple myeloma) and liver cancer cell lines.
Our analysis showed that: 1) Meticrane induced alteration in the cell viability and proliferation in leukemia cells (Jurkat and K562 cells) and liver cancer (SK-hep-1), however, no evidence of apoptosis was detectable. 2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215).
3) A genome-wide transcriptional analysis showed that meticrane treatment induces changes in the expression of genes associated with non-cancer associated pathways. Of importance, differentially expressed genes showed favorable correlation with the survival-related genes in the cancer genome. 4) We also performed molecular docking analysis and found considerable binding affinity scores of meticrane against PD-L1, TIM-3, CD73, and HDACs.
Additionally, we tested its suitability for immunotherapy against cancers, but meticrane showed no response to the cytotoxicity of cytokine-induced killer (CIK) cells. To our knowledge, our study is the first attempt to identify and experimentally confirm the anti-cancer potential of meticrane, being also the first to test the suitability of any non-oncology drug in CIK cell therapy.
Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors.
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