Data on the in vitro and in vivo anti-tumor effects of itraconazole, paclitaxel, and the two in combination in HT-29 and YM-1 cancer cell line and HT-29 colon cancer xenograft models.

Colon cancer is one of the fatal cancers in the world that metastatic potential and resistance to chemotherapy drugs are outstanding causes of cancer-induced mortality [1], [2], [3], [4]. We have investigated in vitro and in vivo anti-cancer effect of itraconazole and paclitaxel alone and their anti-cancer synergistic effect through MTT assay in YM-1 and HT-29 cell lines and in HT-29 tumor-bearing nude mice. Histopathological experiment was done for further assessment. Also, we evaluated the inhibitory effect of itraconazole on P-gp using specific in vivo biodistribution through 99mTc-MIBI uptake. 99mTc-MIBI, a myocardial perfusion imaging agent, is a useful radiotracer in diagnosis of some tumors and the liver and tumor accumulation of 99mTc-MIBI is changed by P-gp regulators [5], [6], [7], [8]. The data presented in this article are related to the research paper entitled "Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice". We hope our preliminary data to be helpful to design the chemotherapy regimen schedule with Itraconazole and Paclitaxel.

Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice.

P-glycoprotein (P-gp), is an important efflux pump involved in chemotherapy resistance in human colon cancer. We investigated the efficacy of itraconazole as a P-gp inhibitor and its therapeutic synergistic relationship to paclitaxel through 99mTc-MIBI accumulation in HT-29 tumor-bearing nude mice. Histopathological screening along with in vitro experiments was done for further assessment. Itraconazole successfully inhibited P-gp mediated 99mTc-MIBI efflux, increasing its in vitro accumulation in itraconazole-receiving dishes. Notably, the co-administration of itraconazole with paclitaxel significantly enhanced the in vitro cytotoxicity effect of paclitaxel in itraconazole + paclitaxel wells containing HT-29 cells. Compared to the control, tumor volume in mice treated with itraconazole, paclitaxel and itraconazole +paclitaxel showed growth suppression approximately by 36.21, 60.02, and 73.3% respectively. And compared to paclitaxel group, the nude mice co-treated with paclitaxel and itraconazole showed suppression of tumor growth by about 33.31 % at the end of the treatment period. Also the biodistribution result showed that the co-administration of itraconazole with paclitaxel raised the mean tumor radioactivity accumulation compared to control and paclitaxel group. When given paclitaxel alone, the ID% of hepatic and cardiac tissue was reduced while co-administration of itraconazole with paclitaxel increased 99mTc-MIBI accumulation in these organs. Furthermore, the histopathological findings confirmed the biodistribution results. These results demonstrate that although monotherapy with itraconazole or paclitaxel has anti-tumor activity against HT-29 human colorectal cancer, a synergistic anti-tumor activity can be achieved when itraconazole is co-administered with paclitaxel. Also, 99mTc-MIBI is an effective radiotracer for monitoring response to treatment in MDR tumors.