Effects of TNF alone or in combination with chemotherapeutic agents on human ovarian cancers in vitro and in nude mice.
Using the tetrazolium (MTT) assay, we examined the cytotoxicities of recombinant human tumor necrosis factor (rhTNF) and five chemotherapeutic agents, namely CTX, 5-FU, VCR, DDP and KSM, on human ovarian cancer cell lines OVCAR3 and CAOV3. The results showed that the cytotoxicities of rhTNF at concentrations of 50-50,000 U/ml on OVCAR3 cell line and CAOV3 cell line exposed to rhTNF for 24 hours were from 14.2% +/- 6.8% to 67.2% +/- 3.0% and from 8.2% +/- 4.3% to 60.9% +/- 1.3%, respectively. The cytotoxicities of all five chemotherapeutic agents tested on the two cell lines were much lower than that of rhTNF. We also studied the combined antitumor potential of rhTNF with the five chemotherapeutic agents and the results showed that there were various degrees of synergism in cytotoxicities of rhTNF in combination with DDP or KSM on the two cell lines. Based on experiments in vitro, the in vivo antitumor activities of rhTNF, both alone and in combination with KSM, were examined in OVCAR3 cancer transplanted in nude mice. The results showed a considerable antitumor effect of rhTNF when it was used alone and a marked synergistic effect when it was used in combination with KSM on the xenograft tumors.
Zhao
E
E
Department of Obstetrics and Gynecology, Chinese Great Wall Hospital, Beijing.
Zhou
M
M
Fu
C
C
Shen
B
B
Zhang
Q
Q
Lian
L
L
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D014750:Vincristine / Q000494:pharmacology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014750:Vincristine; D003520:Cyclophosphamide; D005472:Fluorouracil