Bortezomib Increases the Cancer Therapeutic Efficacy of Poly(amino acid)-Doxorubicin
Bortezomib Increases the Cancer Therapeutic Efficacy of Poly(amino acid)-Doxorubicin
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硼替佐米提高聚氨基酸阿霉素的癌症治疗效果
DOI：
10.1021/acsbiomaterials.7b00639
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发表时间：
2018
影响因子：
--
通讯作者：
Tang ZH
中科院分区：
文献类型：
--
作者：
Shen Na;Jiang Jian;Zhang Dawei;Wang Guanyi;Lv Shixian;Jia Yanjie;Tang Zhaohui;Chen Xuesi;Jiang Jian;Wang Guanyi;Tang ZH
目前，化疗仍然是治疗癌症的主要方法。阿霉素是一种常规的化疗药物，先前的研究表明，mPEG5k-b-P(Glu10-r-Phe10) -阿霉素是一种更优秀的用于癌症治疗的纳米药物，与游离阿霉素相比，它具有治疗优势。因此，本文对阿霉素耐药肿瘤的治疗效果进行了研究。虽然细胞活力和细胞摄取结果并未反映纳米药物在耐药肿瘤中的优势，但比较敏感和耐药肿瘤细胞的遗传表达突出了NFκB。因此采用了临床批准的蛋白酶体抑制剂硼替佐米，该药物可能影响NFκB活性。MTT和流式细胞术结果显示，多胺基酸-阿霉素能提高治疗效果；Western blot结果显示，硼替佐米和多胺基酸-阿霉素能协同降低NFκB的表达。通过活体原位异种移植模型证实了协同作用。因此，硼替佐米不仅在敏感期，而且在耐药期都能提高聚氨基酸-阿霉素的抗癌疗效。这使得硼替佐米和多（氨基酸）-阿霉素的联合治疗成为临床有效的策略和指导。
Currently, chemotherapy is still a primary method to treat cancers. Doxorubicin is a regular chemotherapy drug, and a previous study indicated that mPEG5k-b-P(Glu10-r-Phe10)–doxorubicin is a more excellent nanodrug for cancer therapy, as it created a therapeutic advantage compared with free doxorubicin. Therefore, the efficacy of doxorubicin-resistant tumor treatment was investigated in this paper. While the cell viability and cell uptake results did not reflect an advantage of the nanodrug in drug-resistant tumors, comparison of the genetic expression of sensitive and resistant tumor cells highlighted NFκB. The proteasome inhibitor bortezomib, which is approved clinically and may influence the NFκB activity, was thus employed. The MTT assay and flow cytometry indicated that it could increase the therapeutic efficacy of poly(amino acid)–doxorubicin, and Western blot results showed that bortezomib and poly(amino acid)–doxorubicin can synergistically diminish NFκB expression. The synergism was confirmed through the orthotopic xenograft model in vivo. Thus, bortezomib can enhance the cancer therapeutic efficiency of poly(amino acid)–doxorubicin not only during the sensitive period but also during the resistant period. This makes the combination of bortezomib and poly(amino acid)–doxorubicin a potent strategy and guidance for the clinic.