Calcitriol does not significantly enhance the efficacy of radiation of human cervical tumors in mice

Objective: Calcitriol can enhance the sensitivity of cancer cells to radiation in vitro. The authors aimed to investigate the potential synergistic effect of calcitriol and radiation in a xenograft mouse model of human cervical cancer. Materials and Methods: Tumor-bearing mice were fed with vehicle arachis oil or 2.5 μg/kg calcitriol daily for 15 consecutive days. Some mice received ten Gy radiation on day 7 post treatment. Tumor growth was monitored, and the tumor tissues were examined by histology and electron microscopy. Results: Treatment with either calcitriol or radiation significantly inhibited the growth of implanted cervical cancers (p < 0.05 vs. control) and increased the number of dead tumor cells in the tumor sections. However, there was no significant difference in the tumor weights between the mice with radiation alone and both radiation and calcitriol treatment. Conclusion: Calcitriol had anti-tumoral activity, but failed to enhance the efficacy of radiation in human cervical cancers.

Calcitriol; Cervical tumor; Radiation response.

[1] Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D.: “Global cancer statistics”. CA Cancer J. Clin., 2011, 61, 69.

[2] Tanderup K., Georg D., Potter R., Kirisits C., Grau C, Lindegaard J. C.: “Adaptive management of cervical cancer radiotherapy”. Semin. Radiat. Oncol., 2010, 20, 121.

[3] Klopp A.H., Eifel P.J.: “Chemoradiotherapy for cervical cancer in 2010”. Curr. Oncol. Rep., 2011, 13, 77.

[4] Leitao M.M., Jr., Chi D.S.: “Recurrent cervical cancer”. Curr. Treat. Options Oncol., 2002, 3, 105.

[5] Quinn M.A., Benedet J.L., Odicino F., Maisonneuve P., Beller U., Creasman W.T., et al.: “Carcinoma of the cervix uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int. J. Gynaecol. Obstet., 2006, 95, S43.

[6] Hosono S., Matsuo K., Kajiyama H., Hirose K., Suzuki T., Kawase T., et al.: “Association between dietary calcium and vitamin D intake and cervical carcinogenesis among Japanese women”. Eur. J. Clin. Nutr., 2010, 64, 400.

[7] Deeb K.K., Trump D.L., Johnson C.S.: “Vitamin D signalling path-ways in cancer: potential for anticancer therapeutics”. Nat. Rev. Can-cer, 2007, 7, 684.

[8] Colston K., Colston M.J., Feldman D.: “1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture”. Endocrinology, 1981, 108, 1083.

[9] Bohl L.P., Liaudat A.C., Picotto G., Marchionatti A.M., Narvaez C.J., Welsh J., et al.: “Buthionine sulfoximine and 1,25-dihydroxyvita-min D induce apoptosis in breast cancer cells via induction of reac-tive oxygen species”. Cancer Invest., 2012, 30, 560.

[10] Krishnan A.V., Swami S., Feldman D.: “The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer”. Steroids, 2012, 77, 1107.

[11] Wilson E.N., Bristol M.L., Di X., Maltese W.A., Koterba K., Beck-man M.J., et al.: “A switch between cytoprotective and cytotoxic au-tophagy in the radio sensitization of breast tumor cells by chloroquine and vitamin D”. Horm. Cancer, 2011, 2, 272.

[12] Dunlap N., Schwartz G.G., Eads D., Cramer S.D., Sherk A.B., John V., et al.: “1alpha,25-dihydroxyvitamin D (3) (calcitriol) and its analogue, 19-nor-1alpha,25 (OH) (2)D (2), potentiate the effects of ionising ra-diation on human prostate cancer cells”. Br. J. Cancer, 2003, 89, 746.

[13] Tsoukas C.D., Provvedini D.M., Manolagas S.C.: “1,25-dihydrox-yvitamin D3: a novel immunoregulatory hormone”. Science, 1984, 224, 1438.

[14] Krishnan A.V., Feldman D.: “Mechanisms of the anticancer and anti-inflammatory actions of vitamin D”. Annu. Rev. Pharmacol. Toxicol., 2011, 51, 311.

[15] Jiang F., Bao J., Li P., Nicosia S.V., Bai W.: “Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase”. J. Biol. Chem., 2004, 279, 53213.

[16] Friedrich M., Rafi L., Mitschele T., Tilgen W., Schmidt W., Reichrath J.: “Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer”. Recent Results Cancer Res., 2003, 164, 239.

[17] Friedrich M., Meyberg R., Axt-Fliedner R., Villena-Heinsen C., Tilgen W., Schmidt W., et al.: “Vitamin D receptor (VDR) expression is not a prognostic factor in cervical cancer”. Anticancer Res., 2002, 22, 299.

[18] Saunders D.E., Christensen C., Lawrence W.D., Malviya V.K., Malone J.M., Williams J.R., et al.: “Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms”. Gynecol. Oncol., 1992, 44, 131.

[19] Friedlander M., Grogan M.: “Guidelines for the treatment of recurrent and metastatic cervical cancer”. Oncologist, 2002, 7, 342.

[20] Tang J., Tang Y., Yang J., Huang S.: “Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma”. Gynecol. Oncol., 2012, 125, 297.

[21] Rose P.G., Bundy B.N., Watkins E.B., Thigpen J.T., Deppe G., Maiman M.A., et al.: “Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer”. N. Engl. J. Med., 1999, 340, 1144.

[22] Gadducci A., Tana R., Cosio S., Cionini L.: “Treatment options in recurrent cervical cancer (Review)”. Oncol. Lett., 2010, 1, 3.