Recovering the angiogenic/angiostatic balance in NNK-induced lung carcinoma via 12 weeks of submaximal swimming and Nigella sativa nanocapsule

通过 12 周亚极量游泳和黑种草纳米胶囊恢复 NNK 诱发的肺癌中的血管生成/血管抑制平衡

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作者:Zahra Abrishami Kia, Seyede Tayebeh Sadati Bizaki, Elham Asaádi Ghareh Tapeh, Shadmehr Mirdar Harijani, Nayyereh Katal, Roya Gorji Baziary

Background

Carcinogen nitrosamine 4-(methyl-trosamino)-1-(3-pyridyl)-1-butanone (NNK) remarkably affects the actions of growth factors: EGFR, VEGFR-2, as well as the natural tumor suppressors: TGFβ-1 and TIMP-1. We propose that utilizing non-chemical interventions such as swimming and Nigella sativa nanocapsule play role in controlling cancer progression through direct effects on tumor-inherent factors. Material and

Conclusion

We recommend 12 weeks of submaximal swimming and 125 μg/kg N.sativa nanocapsule are safe interventions to recover the balance of selected angiogenic/ angiostatic markers and to control tumor initiation, growth, and metastasis in lung carcinoma induced by 12/5 mg/kg of NNK injection.

Material and methods

Male rats were randomly placed into seven groups: Control (C), Solvent (S), (NNK), NNK+N.sativa (NNK+NS), NNK+Exercise (NNK+E), N.sativa+Exercise (NS+E), NNK+N.sativa+Exercise (NNK+NS+E). The exercise program consisted of 12 weeks of submaximal swimming. NNK and NS groups received weekly doses of 12/5 mg/kg and 125 μg/kg of NNK and N.sativa, respectively. By the end of the protocol, the levels of VEGFR-2, and TIMP-1 were determined using immunohistochemistry method and EGFR, and TGFβ-1 levels were measured by RT-PCR assay.

Methods

Male rats were randomly placed into seven groups: Control (C), Solvent (S), (NNK), NNK+N.sativa (NNK+NS), NNK+Exercise (NNK+E), N.sativa+Exercise (NS+E), NNK+N.sativa+Exercise (NNK+NS+E). The exercise program consisted of 12 weeks of submaximal swimming. NNK and NS groups received weekly doses of 12/5 mg/kg and 125 μg/kg of NNK and N.sativa, respectively. By the end of the protocol, the levels of VEGFR-2, and TIMP-1 were determined using immunohistochemistry method and EGFR, and TGFβ-1 levels were measured by RT-PCR assay.

Results

In comparison with control group, there was a significant increase in the levels of VEGFR-2 in NNK, NNK+E, NNK+NS, NS+E, and NNK+NS+E groups (P ≤ 0.001), also TGFβ-1 levels of NNK+E and NS+E groups significantly increased (P ≤ 0.001). While EGFR levels did not change remarkably (P˃0.05), except in NNK group (P ≤ 0.001), TIMP-1 in NNK, NNK+E, NS+E, NNK+NS+E groups significantly decreased (P ≤ 0.001).

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