Growth‐inhibitory Effects of N, N‐Diethyl‐2‐[4‐(phenylmethyl)phenoxy]‐ethanamine‐HCl Combined with Cisplatin on Human Ovarian Cancer Cells Inoculated into Nude Mice
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In 5‐day incubation of an estrogen receptor‐negative human ovarian cancer cell line (KF) with diethyl‐2‐[4‐(phenylmethyl)phenoxy]ethanamine‐HCl (DPPE), the concentration of DPPE required for 50% inhibition of KF cell proliferation (IC 50) was 1.7 μM. The IC50 of DPPE for inhibition of protein kinase C (PKC) activity was 3.0 μM, a similar value to those of other antiestrogens such as tamoxifen and clomiphene. DPPE also inhibited phosphorylation of mitogen‐activated protein kinase in KF cells. When treatment with DPPE was started 7 days after inoculation of KF cells into nude mice, 50 mg/kg DPPE alone resulted in a significant growth retardation in the early stage of tumor growth. Although 25 mg/kg DPPE showed a similar effect to 2 mg/kg cisplatin (CDDP), the combination had the most marked tumor growth‐inhibitory effect. Nude mice treated with combinations of CDDP and DPPE survived significantly longer than not only untreated, but also CDDP‐alone‐treated mice, while 50 mg/kg but not 25 mg/kg DPPE alone had an effect comparable to that of 2 mg/kg CDDP alone. If treatment with DPPE was begun from the day after tumor inoculation, the inhibitory effect of DPPE was further enhanced, especially when combined with CDDP. If treatment with DPPE was started in nude mice with a lower tumor burden, 25 mg/kg as well as 50 mg/kg DPPE had a similar effect to 2 mg/kg CDDP, in terms of survival. When DPPE was combined with CDDP, the effect was significantly enhanced, compared to that of either alone. These treatments could be done without any adverse side effect. Thus, we conclude that DPPE has an antiestrogen action and its tumor growth‐inhibiting activity is enhanced on administration in combination with CDDP.
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- Authors
- Hiramatsu, H., Kikuchi, Y., Kudoh, K., Kita, T., Tode, T., & Nagata, I.
- Affiliations
- National Defense Medical College Hospital (JP)
- Corresponding author
- Kikuchi, Yoshihiro
- ORCID
- Nagata, Ichiro
- Venue
- Japanese Journal of Cancer Research
- Publisher
- Wiley
- Published
- 1997-10
- Volume
- 88
- Issue
- 10
- Pages
- 1003-1008
- ISSN
- 0910-5050 (ISSN-L)
- PMC
- PMC5921275
- OpenAlex
- W1973882178
- Cited by
- 5
- References
- 17
- Citations by year
- 2015: 1
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Japanese Journal of Cancer Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- dppe, antiestrogens, cisplatin, ovarian cancer, combination chemotherapy, protein kinase C inhibition, mitogen-activated protein kinase phosphorylation, tumor growth inhibition, tumor burden, survival
- MeSH terms
- Animals, Antineoplastic Agents, Cell Division, Cisplatin, Clomiphene, Drug Combinations, Female, Humans, Mice, Nude, Neoplasm Transplantation, Ovarian Neoplasms, Phenyl Ethers, Phosphorylation, Protein Kinase C, Tamoxifen, Tumor Cells, Cultured, Survival Rate, Calcium-Calmodulin-Dependent Protein Kinases, Mice
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