ONCOmmunity

Synergistic Effects of Olaparib and DNA-damaging Agents in Oesophageal Squamous Cell Carcinoma Cell Lines.

By: Keisuke Miyamoto, Tetsuya Minegaki, Mami Tanahashi, Ayaka Yamamoto, Yumi Moriyama, Akari Wada, Ayaka Matsumoto, Keisuke Ota, Mai Tanaka, Utako Masuda, Masayuki Tsujimoto, Kohshi Nishiguchi

Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.
2019-01-22; doi: 10.21873/anticanres.13288

Abstract

Background/aim

Chemotherapy is an important first-line treatment for oesophageal squamous cell carcinoma (ESCC). However, there are few secondary options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, enhances the cytotoxicity of various anticancer drugs and has been used to treat advanced ovarian and breast cancers. This study examined the effect of olaparib on the cytotoxicity of anticancer drugs in ESCC cell lines.

Materials

ESCC KYSE70 and KYSE140 cells were grown in Dulbecco's modified Eagle's medium and treated with 5-fluorouracil (5-FU), cisplatin, docetaxel, doxorubicin, SN-38, or temozolomide without or with olaparib.

Results

Olaparib enhanced the cytotoxicity of all tested anticancer drugs and increased the effects of cisplatin, doxorubicin, SN-38, and temozolomide synergistically. These anticancer drugs caused the accumulation of phospho-histone H2AX Ser139 (γH2AX), a biomarker of DNA damage, and olaparib increased this accumulation.

Conclusion

PARP inhibitors may potentiate the anticancer activity of DNA-damaging agents in ESCC patients synergistically.