The Functions Of4-methyl-3-nitro-benzoic Acid On Tumor Migration And Metastasis

ObjectiveMalignant tumor is a serious disease which occurred commonly and frequently. Cancer metastasis is the most essential features of the tumor biological behavior. Thus, during the treatment of cancer, controlling tumor invasion and metastasis is the most important problems. Although there are some anti-tumor invasion and metastasis drugs applied in the clinical, still have some problems such as:low effective rate, poorly selectivity, big side effects and drug resistance. It is important to search for low toxicity, high efficient drugs to treat tumor invasion and metastasis.Previous results of our groups demonstrated that4-methyl-3-nitro-benzoic acid (MNB A) can inhibit the migration of tumor cells by high-flux selection. In this study, we will further demonstrated the functions of MNBA on tumor cells migration and metastasis both in vivo and in vitro.The study was designed to study the role of MNBA on breast cancer migration and its mechanism, provided theoretical basis and experiment evidence for researching and developing effective drug for the treatment of liver cancer.Methods1) Using MTT assay and flow cytometry assay to detect the cytotoxicity and the synergistic effects combinated with Paclitaxel in human breast cancer cell lines MCF-7, MDA-MB-231and human non-small cell lung cancer cell line A549.2) Chemotasis assay, adhesion assay and wound healing assay detected the migration inhibition effects of MNBA in MCF-7cells, MDA-MB-231cells and A549cells.3) F-actin polymerization assay to study the influence of MNBA on cells actin polymerization in A549cells. Western blotting assay detected the expression of phospho-cofilin in MNBA treated cells and control cells.4) Investigating the role of MNBA in preventing breast cancer growth and metastasis directly or synergistically with Paclitaxel in vivo.Results 1) MNB A have no effect on the proliferation and cell cycles of breast cancer cells and NSCLC cells after treated for24hours. MNBA can synergistically enhance the functions of Paclitaxel on inhibiting tumor cells proliferation (P<0.05).2) MNBA can significantly inhibit the chemotaxis and migration abilities of breast cancer cells and NSCLC cells after treated for24hours (P<0.05). But have no effect on the EGFR expression.3) MNBA can significantly inhibit the adhesion of breast cancer cells and NSCLC cells after treated for24hours (P<0.05).4) MNBA can decreased actin polymerization ability compared with the control cells after treated for24hours (P<0.05). Western blotting assay demonstrated that MNBA can impair the expression of phospho-cofilin which is related to actin polymerization.5) In vivo breast cancer transplanted tumor models, high dose groups of MNBA can inordinately inhibited breast cancer cells growth and synergistically enhance the functions of Paclitaxel on inhibiting tumor growth. At the same time, MNBA can inhibit the metastasis of breast cancer in vivo.Conelusions1) MNBA is a kinds of low toxicity drugs and have no effect on tumor cells proliferation. It can synergistically enhance the functions of Paclitaxel on inhibiting tumor cells proliferation2) MNBA can significantly inhibit EGF-induced chemotaxis and migration of breast cancer cell and NSCLC cells. MNBA probably regulate the activation of cofilin to control cytoskeleton rearrangement.3) The functions of MNBA on tumor growth and metastasis provide theory evidence for new drugs which is efficient and low toxicity on anti-tumor metastasis.