Intratumoral injection of cisplatin in various concentrations of ethanol for cisplatin-resistant lung tumors

Abstract

Abstract. Cisplatin [cis-diammineplatinum dichloride (DDP)] resistance is a major limitation in the treatment of lung cancer. We previously demonstrated that DDP dissolved in 5% ethanol (5% ethanol-DDP) injected intratumorally was able to eradicate DDP-resistant lung tumors and prolong survival, as 5% ethanol improved DDP delivery to the tumor. The present study aimed to investigate the efficacy of DDP in various concentrations of ethanol and determine the optimal ethanol concentration in which DDP exhibits optimal efficacy in reducing tumor volume and prolonging survival. The efficiency of DDP dissolved in 2, 5, 10, 20 and 50% ethanol (v̸v) in DDP-resistant A549̸DDP lung tumor-bearing Balb̸C nude mice was investigated. Tumor growth and survival were evaluated in all the treatment groups. Microvessel density in xenograft tumor tissues was measured by immunohistochemistry. Our results revealed that 5% ethanol-DDP exhibited the highest efficiency in reducing tumor volume and prolonging survival among all the investigated ethanol-DDP combinations. We found that 5% ethanol-DDP produced the most significant inhibition of tumor angiogenesis among all the remaining ethanol-DDP combinations, while treatment with ethanol alone increased tumor angiogenesis. In conclusion, 5% ethanol-DDP produced the strongest tumor growth inhibition and longest survival among all the investigated ethanol-DDP combinations, possibly providing a novel therapeutic strategy for improving the survival of patients with DDP-resistant lung cancer. The potent inhibition of tumor angiogenesis by 5% ethanol-DDP may be one of the mechanisms underlying its superior efficiency.

The effect of tetrandrine combined with cisplatin on proliferation and apoptosis of A549/DDP cells and A549 cells

“…Although this is the best available at present, it remains impossible to predict which patients will respond to chemotherapy. Moreover, most NSCLC tumors develop drug resistance [2]. Because cisplatin-based chemotherapy has been the first-line treatment for NSCLC in the clinic [3], the effect of cisplatin on lung cancer has been widely studied.…”