Pluronic, a
poly(ethylene oxide)-poly(propylene oxide)-poly (ethylene oxide) block copolymer, has been shown to enhance the cytotoxic activity of anticancer drugs in various cell lines. In the current study the effect of
Pluronic P85 (P85) and
Pluronic L61 (L61) on the intratumoral
chemotherapy of an experimental
adenocarcinoma in rats was examined. A total of 120 subcutaneous
tumors (4 per rat) were inoculated in 30 BDIX rats and were treated weekly for 4 weeks with intratumoral injection of
carboplatin (
CPt) alone or with either P85 or L61.
Tumors were monitored weekly and were excised at the endpoint for histologic evaluation. The effect of
Pluronic on levels of intracellular
ATP was explored as a possible mechanism of sensitization. Results showed that
tumors treated with low-dose
CPt (2.8 mg/kg) and P85 or L61 exhibited significant reductions in
tumor volume after 28 days relative to Day 0 (112.7% +/- 34.4%, n = 15; 131.3% +/- 55.6%, n = 8) compared with
tumors treated with free
drug (339.4% +/- 75.0%, n = 16). Control
tumors treated with either P85 or L61 alone or with saline showed volume increases of 1079.4% +/- 143.6% (n = 16), 729.4% +/- 202.2% (n = 7), and 1119.2% +/- 6.1% (n = 16), respectively. Treatment with high-dose
CPt (20.7 mg/kg) led to a 79.3% +/- 4.2% reduction in
tumor volume, and no differences were noted with addition of P85 or L61. In vitro
ATP measurements showed that 28.0 mg/kg of P85 significantly reduced levels of intracellular
ATP to 44.7% +/- 1.5% of controls, whereas L61 at this concentration depleted
ATP levels completely. Results confirm that
Pluronic P85 and L61 act as potent sensitizers to
carboplatin chemotherapy of the experimental
colorectal carcinoma, leading to a significant reduction of
tumor growth compared to
carboplatin alone.
ATP depletion is a possible mechanism for these observed differences.