Cytotoxic effects of the newly-developed chemotherapeutic agents 17-AAG in combination with oxaliplatin and capecitabine in colorectal cancer cell lines

The use of heat shock protein 90 inhibitors like 17-allylamino-17-demethoxy-geldanamycin (17-AAG) has
been recently introduced as an attractive anticancer therapy. It has been shown that 17-AAG may potentiate
the inhibitory effects of some classical anticolorectal cancer (CRC) agents. In this study, two panels of
colorectal carcinoma cell lines were used to evaluate the effects of 17-AAG in combination with
capecitabine and oxaliplatin as double and triple combination therapies on the proliferation of CRC cell
lines. HT-29 and all HCT-116 cell lines were seeded in culture media in the presence of different doses of
the mentioned drugs in single, double, and triple combinations. Water-soluble tetrazolium-1 (WST-1) assay
was used to investigate cell proliferation 24 h after treatments. Then, dose-response curves were plotted
using WST-1outputs, and IC50 values were determined. For double and triple combinations respectively 0.5
× IC50 and 0.25 × IC50 were used. Data was analyzed with the software CompuSyn. Drug interactions were
analyzed using Chou-Talalay method to calculate the combination index (CI).The data revealed that 17-AAG
shows a potent synergistic interaction (CI < 1) with oxaliplatin and capecitabine in double combinations (0.5
× IC50) in both cell lines. In the case of triple combinations, the findings showed an antagonistic interaction
(CI > 1) in HT-29 and a synergistic effect (CI < 1) in HCT-116 (0.25 × IC50) cell lines. It was concluded that
double combinations of 17-AAG with oxaliplatin or capecitabine might be effective against HCT-116 and
HT-29 cell lines. However, in triple combinations, positive results were seen only against HCT-116. Further
investigation is suggested to confirm the effectiveness of these combinations in clinical trials.