Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Endometrial Cancer Cells In Vitro.

BACKGROUND/AIM Endometrial cancer cells are known to be sensitive to carboplatin and paclitaxel. Furthermore, vitamin D (1,25-D3) has been reported to inhibit endometrial cancer cell growth both as a single agent and combined with carboplatin. However, there are no studies comparing the effect of paclitaxel and carboplatin as single agents vs. in combination in endometrial cancer cell lines. Neither has the effect of 1,25-D3 been studied with paclitaxel. The present study investigated the effect of paclitaxel, carboplatin and 1,25-D3 on the growth of endometrial cancer cells in vitro. MATERIALS AND METHODS Two endometrial adenocarcinoma cell lines (UT-EC-1 and UT-EC-3) were cultured with different doses of paclitaxel, carboplatin and 1,25-D3. The cellular VDR (vitamin D receptor) mRNA levels were measured and the expression of estrogen (ER) and progesterone (PR) receptors by the cells was determined. RESULTS In the UT-EC-1 cell line the growth inhibition was 72% with paclitaxel, 54% with carboplatin and 73% with the combination of these compounds. The corresponding numbers in UT-EC-3 were 70%, 33% and 65%, respectively. 1,25-D3 suppressed cell growth 88% with paclitaxel, 63% with carboplatin and 87% with their combination in the UT-EC-1 cell line. CONCLUSION In both cell lines, single-agent paclitaxel was as effective as the combination of the compounds and more effective than single carboplatin. 1,25-D3 may further contribute to the cytotoxic effect of these agents.

[1]  I. Vergote,et al.  Phase II study of weekly paclitaxel/carboplatin in combination with prophylactic G-CSF in the treatment of gynecologic cancers: A study in 108 patients by the Belgian Gynaecological Oncology Group. , 2015, Gynecologic oncology.

[2]  Mitsuaki Suzuki,et al.  What is an appropriate second-line regimen for recurrent endometrial cancer? Ancillary analysis of the SGSG012/GOTIC004/Intergroup study , 2015, Cancer Chemotherapy and Pharmacology.

[3]  J. Welsh,et al.  Modeling vitamin D actions in triple negative/basal-like breast cancer , 2014, The Journal of Steroid Biochemistry and Molecular Biology.

[4]  Sandro Santagata,et al.  Taxonomy of breast cancer based on normal cell phenotype predicts outcome. , 2014, The Journal of clinical investigation.

[5]  T. Conrads,et al.  Progesterone Enhances Calcitriol Antitumor Activity by Upregulating Vitamin D Receptor Expression and Promoting Apoptosis in Endometrial Cancer Cells , 2013, Cancer Prevention Research.

[6]  C. Presant,et al.  Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment. , 2010, Journal of gynecologic oncology.

[7]  P. Heinonen,et al.  Vitamin D inhibits myometrial and leiomyoma cell proliferation in vitro. , 2009, Fertility and sterility.

[8]  J. Kim,et al.  Chemosensitization of endometrial cancer cells through AKT inhibition involves FOXO1. , 2008, Gynecologic oncology.

[9]  A. Kallioniemi,et al.  A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7 , 2007, Breast Cancer Research and Treatment.

[10]  R. Mehta,et al.  Overexpression of ER and VDR is not sufficient to make ER-negative MDA-MB231 breast cancer cells responsive to 1alpha-hydroxyvitamin D5. , 2006, Carcinogenesis.

[11]  R. Barakat,et al.  Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study , 2006, International Journal of Gynecologic Cancer.

[12]  R. Mehta,et al.  Growth inhibition of carcinogen-transformed MCF-12F breast epithelial cells and hormone-sensitive BT-474 breast cancer cells by 1alpha-hydroxyvitamin D5. , 2006, Carcinogenesis.

[13]  J. Welsh,et al.  Vitamin D receptor status alters mammary gland morphology and tumorigenesis in MMTV-neu mice. , 2004, Carcinogenesis.

[14]  P. Hershberger,et al.  Anti-tumor activity of calcitriol: pre-clinical and clinical studies , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[15]  S. Miettinen,et al.  Expression of Nuclear Receptors and Cofacotrs in Human Endometrium and Myometrium , 2004, The Journal of the Society for Gynecologic Investigation: JSGI.

[16]  V. Rantanen,et al.  Mutations of TP53 do not correlate with the sensitivity to paclitaxel--a study using 27 gynaecological cancer cell lines. , 2002, European journal of cancer.

[17]  J. Reichrath,et al.  Immunohistochemical analysis of 1,25-dihydroxyvitamin-D3-receptors, estrogen and progesterone receptors and Ki-67 in ovarian carcinoma. , 2002, Anticancer research.

[18]  K. Swenerton,et al.  Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  R. Edwards,et al.  A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. , 1997, Seminars in oncology.

[20]  M. Brattain,et al.  Modulation of cell cycle control by vitamin D3 and its analogue, EB1089, in human breast cancer cells , 1997, Oncogene.

[21]  M. Hirata,et al.  Vitamin D Receptor in Endometrial Carcinoma and the Differentiation‐Inducing Effect of 1,25‐Dihydroxyvitamin D3 on Endometrial Carcinoma Cell Lines , 1996, The journal of obstetrics and gynaecology research.

[22]  D. Mutch,et al.  A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. , 1996, Gynecologic oncology.

[23]  J. Jones,et al.  Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. , 1996, Cancer research.

[24]  L. Freedman,et al.  Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. , 1996, Genes & development.

[25]  V. Rantanen,et al.  Comparative evaluation of cisplatin and carboplatin sensitivity in endometrial adenocarcinoma cell lines. , 1994, British Journal of Cancer.

[26]  J. Kavanagh,et al.  Treatment of advanced or recurrent endometrial carcinoma with single-agent carboplatin. , 1993, Gynecologic oncology.

[27]  M. Deppe,et al.  Additive inhibition of RL95-2 endometrial carcinoma cell growth by carboplatin and 1,25 dihydroxyvitamin D3. , 1993, Gynecologic oncology.

[28]  S. Grénman,et al.  Establishment and characterization of UM-EC-2, a tamoxifen-sensitive, estrogen receptor-negative human endometrial carcinoma cell line. , 1990, Gynecologic oncology.

[29]  S. Grénman,et al.  In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate. , 1988, Gynecologic oncology.

[30]  Jason D. Wright,et al.  Comparative Performance of the 2009 International Federation of Gynecology and Obstetrics' Staging System for Uterine Corpus Cancer. , 2011, Obstetrics and gynecology.

[31]  M. Friedrich,et al.  Expression of 25 hydroxyvitamin D3-1alpha-hydroxylase in human endometrial tissue. , 2007, The Journal of steroid biochemistry and molecular biology.

[32]  L. J. Schelven.  Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study , 2004 .

[33]  J. Welsh,et al.  Comparative effects of 1,25(OH)2D3 and EB1089 on cell cycle kinetics and apoptosis in MCF-7 breast cancer cells , 2004, Breast Cancer Research and Treatment.

[34]  S. Miettinen,et al.  Antiproliferative action of vitamin D. , 2002, Vitamins and hormones.

[35]  D. Thurnher,et al.  1,25(OH)2 vitamin D3 induces elevated expression of the cell cycle-regulating genes P21 and P27 in squamous carcinoma cell lines of the head and neck. , 2001, Acta oto-laryngologica.

[36]  V. Rantanen,et al.  Endometrial cancer cell lines are sensitive to paclitaxel. , 1996, Anticancer research.

[37]  J. Welsh,et al.  Role of apoptosis in the growth inhibitory effects of vitamin D in MCF-7 cells. , 1995, Advances in experimental medicine and biology.

[38]  M. Haussler,et al.  Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis. , 1991, Cancer research.