[FABP5 promotes cell growth, invasion and metastasis in cervical cancer].

ABSTRACT

Objective: To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer. Methods: The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stage Ⅰa2-Ⅱa2 and 40 cases of normal cervical tissues by real-time PCR and Western blotting. Then, the cells were infected with lentivirus-mediated siRNA-targeting FABP5. CCK-8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on in vitro cell proliferation, migration and invasion. And in vivo xenograft model and lung metastasis model were used to observe the transplanted tumor growth and metastasis in female athymic nude mice. Furthermore, the total protein and RNA were extracted from the primary xenografts to determine the expression levels of FABP5, metalloproteinase-2 and metalloproteinase-9 using Enzyme linked immunosorbent assay (ELISA), real-time PCR and Western blotting. Results: FABP5 expression was found to be significantly unregulated in cervical cancer tissues than that in normal cervical tissues (P<0.05). Compared with the Siha-NC group and uninfected group, the expression of FABP5 mRNA and protein in Siha-FABP5-RNAi group was significantly inhibited along with the decrease of cell proliferation, colony formation, wound healing and invasion ability. The clone formation rates of Siha cells in uninfected group, Siha-NC group and Siha-FABP5-RNAi group were (84.6±4.5)%, (84.6±5.1)% and (21.2±2.6)%, respectively. Moreover, the transwell assay showed that invasive cells in three groups were (72.8±4.7)/HPF, (72.6±3.3)/HPF and (21.4±2.3)/HPF, respectively. All of the difference was statistically significant (P<0.05). Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in nude mice in vivo (P<0.001). The subcutaneously xenografted volume in uninfected group, Siha-NC group and Siha-FABP5-RNAi group was (921.4±63.0) mm(3,) (1 021.4±56.0) mm(3) and (139.6±36.0) mm(3,) respectively. The real-time quantitative PCR results showed that the relative expression levels of MMP-2 and MMP-9 mRNA were 1.00±0.10 and 1.00±0.10, 1.00±0.10 and 1.00±0.10 as well as 0.34±0.13 and 0.38±0.17 in xenografted tumor tissues of uninfected group, Siha-NC group and Siha-FABP5-RNAi group, respectively. MMP-2 and MMP-9 was significantly downregulated after FABP5 inhibition(P<0.05). Additionally, the protein expression trend of MMP-2 and MMP-9 in three groups was consistent with the mRNA levels. Conclusion: FABP5 might promote the carcinogenesis and metastasis of cervical cancer via up-regulating MMP-2 and MMP-9.