Dataset for: Peptide fragments of Hsp70 modulate its chaperone activity and sensitize tumor cells to anti-cancer drug

Most of Hsp70 chaperone inhibitors exert anti-cancer effects and though their toxicity prompted us to employ peptide fragments of the chaperone as its safer modulators and as complements to customary drugs. One of such peptides, ICit-2 was found to inhibit substrate-binding and refolding activities of the chaperone. Using various approaches, we established that ICit-2 binds Hsp70 that may explain the compound inhibitory action. ICit-2 penetrates living A-431 cancer cells and in combination with doxorubicin enhances the drug cytotoxicity and growth inhibitory effect. Similarly, using B16 mouse melanoma model we found that ICit-2 inhibited the rate of tumor growth by 48% compared with the doxorubicin alone proving that the peptide can be employed to sensitize resistant tumors to cytostatic medicines.

绝大多数热休克蛋白70（Hsp70）分子伴侣抑制剂均可发挥抗癌活性，但鉴于其毒性缺陷，我们转而采用该分子伴侣的肽片段作为更安全的调节剂，并作为常规药物的补充制剂。其中一种肽段ICit-2被证实可抑制该分子伴侣的底物结合与重折叠活性。通过多种实验手段，我们确认ICit-2可结合Hsp70，这一机制或可解释该化合物的抑制作用。ICit-2能够穿透活的A-431癌细胞，与阿霉素联合使用时，可增强该药物的细胞毒性与肿瘤生长抑制效果。同样，在B16小鼠黑色素瘤模型中我们发现，相较于单独使用阿霉素，ICit-2可将肿瘤生长速率降低48%，这证明该肽段可用于使耐药肿瘤对细胞抑制类药物增敏。