Managing MMP-2, MMP-9, VEGFR-2, TGFβ-1, and TIMP-1 in NNK-induced lung carcinoma by nonchemical interventions in female rats

Abstract

Background: Smart and flexible methods are attracting remarkable interest in cancer-related biological and chemical therapies. To achieve a safer, affordable, and more effective cancer treatment, we evaluated the application of submaximal swimming and Nigella sativa (NS) nano-drug on lung tissues of female rats induced by NNK. Material and methods: A 12-weeks protocol of submaximal swimming was performed in pathologic and non-pathologic groups. NNK and NS groups, respectively received weekly doses of 12/5 mg/kg and 125 μg/kg of body weight. By the end of the protocol, the ratios of MMP-2, MMP-9, and TIMP-1 determined by using immunohistochemistry essay, and RT-PCR analysis for VEGFR-2 and TGFβ-1. Results: As a result, treatment with exercise and NNK resulted in VEGFR-2 overexpression (P ≤ 0.001 and P ≤ 0.05, respectively). In NNK, NNK+E, NNK+NS, and NNK+NS+E groups, protein expression of MMP-2 and MMP-9 significantly increased, despite the reduction of TIMP-1 levels in the same groups compared to control (P ≤ 0.001). TGFβ-1 ratio significantly increased following preformed interventions in non-pathologic groups: E (P ≤ 0.001) and NS+E (P ≤ 0.01). Conclusion: IHC and gene assays indicate a favorable and acceptable effect of the designed training protocol besides the treatment with N.sativa nano-drug, by which cancer development could be restricted through recovering the natural balance of angiogenic and angiostatic markers.

Keywords

• MMP-2
• MMP-9
• Nigella sativa
• NNK
• Submaximal swimming exercise
• TGFβ-1