Abstract
Background: Long term cisplatin is active in highly cisplatin-resistant cancer cells; however, there is little evidence for its resistant activity in lung cancer with cisplatin. Many mechanisms of cisplatin resistance have been proposed.
Aims: The mechanisms of the long term of cisplatin-resistant lung cancer for histone deacetylase 1（HDAC1）activity is unknown. The long term of cisplatin was used to analyze cisplatin-resistant non-small cell lung cancer cell growth （NSCLC）.
Methods: Western blot was used to analyze cell cycle-related proteins at 24 h and 48 h. Cancer cell viability was measured with MTT assay. Histone deacetylase 1 transfected non-small cell lung cancer cells were used to analyze the direct binding between cytosol and nucleus distribution. Here, using cell viability and migration methods we firstly found cisplatin-resistant lung cancer cells growth by targeting histone deacetylase 1 at 24 h and 48 h. Expression of cisplatin was negatively correlated with HDAC1. And HDAC1 inhibitor, VPA, in the cancer cells were predicted.
Results: Further experiments confirmed that HDAC1 directly targeted E2F and cisplatin at 24 h. Besides, HDAC1 and cisplatin inhibited NSCLC cell growth and reduced expression of E2F and Cyclin E proteins at 48 h. The long-term compromised cisplatin-induced E2F suppression and cancer cell growth. NSCLC cancer cells co-transfected with HDAC1 had a higher cell cycle proliferation at 24 h.
Conclusion: Taken all together, cisplatin interferes with DNA replication kills the cancer cell proliferation; however, long term increased toxification invalid effects of cisplatin, inhibition of apoptosis and DNA repair, induced cisplatin resistance.