恶性肿瘤中IGFBP-rP1的抑癌基因作用机制及其可能的临床实用价值

Mechanism as Tumor Suppressor Gene and Possible Clinical Practical Value of IGFBP-rP1 in Malignant Neoplasm

胰岛素样生长因子结合蛋白相关蛋白1(IGFBP-rP1)是近年来恶性肿瘤的研究热点。本文主要综述IGFBP-rP1在恶性肿瘤中的抑癌基因作用机制及可能的临床实用价值。IGFBP-rP1在恶性肿瘤中的作用广泛涉及细胞的增殖、衰老、凋亡、分化、血管生成等多方面,研究指出IGFBP-rP1可缩短细胞增殖周期并影响非停泊性生长从而抑制增殖。降低致瘤能力;调节BRAF-MEKERK信号通路及pRB、HSP60等相关蛋白的表达从而影响衰老及凋亡;主要通过IGF依赖方式抑制血管生成;而且IGFBP-rP1表达下降跟肿瘤细胞分化程度降低有关。研究显示IGFBP-rP1有一定的临床实用价值,如其表达量跟恶性肿瘤的进展相关,低表达提示某些化疗药物抵抗,可提示预后。而在恶性肿瘤中特异性地上调IGFBP-rP1,可抑制肿瘤增殖及血管生成、诱导细胞衰老凋亡、提高肿瘤分化程度及化疗敏感性,具有治疗意义,但研究者们还在努力探究,争取早日找到一种临床有效的靶向IGFBP-rP1的基因治疗方法。

Insulin-like growth factor binding protein-related protein 1 （ IGFBP-rP1 ） was found to be related to a variety of malignant neo- plasms in recent years. In vivo, IGFBP-rP1 was demonstrated to play a potential tumor suppressor role in most malignant neoplasms. This arti- cle mainly reviewed the mechanism as tumor suppressor genes and possible clinical practical value of IGFBP-rP1 in malignant neoplasms. IG- FBP-rP1 was widely involved in cell proliferation, apoptosis, differentiation, senescence, angiogenesis, et al. The studies pointed out that IG- FBP-rP1 inhibited cell proliferation by shortening the cell cycle and affecting non anchor growth, and then reduced the tumorigenic ability;af- fected tumor cell senescence and apoptosis by adjusting the BRAF-MEK-ERK signaling pathway and the expression of pRB and HSP60 pro- tein ; inhibited angiogenesis mainly through IGF-depended way ; and it＇s lower expression was associated with lower cell differentiation degree. IGFBP-rP1 may have clinical practical value, as it＇s expression related to the progression of the malignant neoplasm,as lower expression prompted some chemotherapy drug resistance and poorer prognosis. Up-regulating IGFBP-rP1 specifically in the malignant neoplasm would lead to inhibition of tumor proliferation and angiogenesis, induction of cell apoptosis, differentiation, senescence, and improvement of chemo- therapy sensitivity. The researchers were trying to find an IGFBP-rP1 targeted gene therapy which can be used in clinical.