Anti-tumor activity of heptaplatin in combination with 5-fluorouracil or paclitaxel against human head and neck cancer cells in vitro.
Heptaplatin (HTP), a newly developed platinum analog, has been approved for the treatment of gastric cancers in South Korea. In this study we explored the potential of HTP for the treatment of head and neck squamous cell cancers (HNSCC). The anti-proliferative activity of HTP was evaluated in FaDu, a human HNSCC cell line. Combinations of HTP with 5-fluorouracil (5-FU) or paclitaxel (PTX) were determined using combination indexes, and were compared with combinations of cisplatin and 5-FU or PTX. In order to evaluate the transport of HTP into tumor tissue, its penetration through multicell layers (MCLs) of cancer cells was measured. Cisplatin+5-FU and HTP+5-FU showed additive to antagonistic interactions. In terms of the HTP+paclitaxel combination, HTP showed antagonism and additivity at the 50 and 80% growth inhibition levels, respectively. An additive interaction was obtained and apoptosis was increased by 2-fold at both inhibition levels when the combinatorial PTX dose was reduced to 1/10. HTP, but not cisplatin or oxaliplatin (L-OHP), maintained its anti-proliferative activity after MCL penetration at clinically relevant concentrations, which can be attributed to lower protein binding of HTP. In conclusion, the present study suggests that low-dose PTX may sensitize tumor cells to HTP. HTP also showed greater penetration through multilayers of tumor cells compared to cisplatin and L-OHP, which may be an important characteristic for solid tumor treatment. Overall, the present study supports the clinical development of HTP in combination with low-dose PTX against HNSCC.
Lee
Jung-Won
JW
Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Park
Jong-Kook
JK
Lee
Sin-Hyung
SH
Kim
Seong-Yun
SY
Cho
Yong-Baik
YB
Kuh
Hyo-Jeong
HJ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004347:Drug Interactions; D005472:Fluorouracil / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008314:Malonates / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D008314:Malonates; D009944:Organoplatinum Compounds; C090717:SKI 2053R; D017239:Paclitaxel; D005472:Fluorouracil