Bortezomib Increases the Cancer Therapeutic Efficacy of Poly(amino acid)–Doxorubicin,ACS Biomaterials Science & Engineering

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Bortezomib Increases the Cancer Therapeutic Efficacy of Poly(amino acid)–Doxorubicin
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2017-11-02 00:00:00 , DOI: 10.1021/acsbiomaterials.7b00639
Na Shen ₁ , Jian Jiang _{1,

2} , Dawei Zhang ₁ , Guanyi Wang _{1,

3} , Shixian Lv ₁ , Yanjie Jia ₁ , Zhaohui Tang ₁ , Xuesi Chen ₁

Affiliation

Currently, chemotherapy is still a primary method to treat cancers. Doxorubicin is a regular chemotherapy drug, and a previous study indicated that mPEG_5k-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.

中文翻译：

硼替佐米提高聚氨基酸阿霉素的抗癌作用

目前，化学疗法仍然是治疗癌症的主要方法。阿霉素是常规化疗药物，先前的研究表明mPEG _5k - b -P（Glu ₁₀ - r -Phe ₁₀）–阿霉素是用于癌症治疗的更出色的纳米药物，因为与游离阿霉素相比，阿霉素具有治疗优势。因此，本文研究了对阿霉素耐药的肿瘤的治疗效果。虽然细胞活力和细胞摄取结果并未反映出纳米药物在耐药性肿瘤中的优势，但对敏感和耐药性肿瘤细胞的基因表达的比较突出了NFκB。因此，使用了经临床批准并可能影响NFκB活性的蛋白酶体抑制剂硼替佐米。MTT分析和流式细胞术表明它可以提高聚氨基酸-阿霉素的治疗效果，蛋白质印迹结果表明硼替佐米和聚氨基酸-阿霉素可以协同减少NFκB的表达。通过体内原位异种移植模型证实了协同作用。因此，硼替佐米不仅可以在敏感期而且可以在耐药期提高聚氨基酸阿霉素的癌症治疗效率。这使得硼替佐米和聚氨基酸-阿霉素的结合成为临床的有效策略和指导。

更新日期：2017-11-03

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