In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3

Pourgholami, Mohammad H.; Akhter, Javed; Lu, Ying; Morris, David L.

doi:10.1016/s0304-3835(99)00416-4

Cited by 58 publications

(45 citation statements)

References 22 publications

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“…1,25-dihydroxyvitamin D3 has been shown to inhibit proliferation of human HCC cell lines that express vitamin D receptor; however, 1,25-dihydroxyvitamin D3 does not show antiproliferative effects on cell lines that do not express the receptor (Miyaguchi and Watanabe, 2000). Chronic treatment of a hepatoblastoma cell line, HepG2, with 1,25-dihydroxyvitamin D3 leads to the inhibition of cell proliferation (Pourgholami et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma in Txnip-deficient mice

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma in Txnip-deficient mice

et al. 2006

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“…Three adjacent restriction polymorphic sites in the VDR gene, the BsmI (rs1544410, A-G base change, designate as genotype B/B, B/b, b/b), ApaI (rs7975232, G-T base change, designate as genotype A/A, A/a, a/a) and TaqI (rs731236, T-C base change, designate as genotype T/T, T/t, t/t), have been reported and extensively studied in several diseases. 17 Although VDR gene variant of genotype t/t was reported to be associated with HBV clearance and active form of vitamin D was shown to inhibit HCC cell proliferation in vitro and in vivo, 19,20 the association of VDR gene polymorphisms with distinct clinical phenotypes of chronic HBV carriers remain largely unclear. Taking advantage of rampant HBV infection in Taiwan, the aim of this study is to investigate the association of VDR gene polymorphisms with distinct clinical phenotypes of Taiwanese chronic HBV carriers as well as the risk of HCC development.…”

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confidence: 99%

Vitamin D receptor gene polymorphisms and distinct clinical phenotypes of hepatitis B carriers in Taiwan

et al. 2009

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Vitamin D exhibits immunomodulatory and antiproliferative effects through vitamin D receptor (VDR) in chronic infections and cancers. We genotyped the BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) polymorphisms of VDR gene in 250 Taiwanese chronic hepatitis B virus (HBV) carriers who were categorized into six phenotypes. After adjustment for age and sex, the frequencies of the VDR B/b, B/a, B/T, B/a/T in patients with hepatitis flare(s) were lower than those without (7 vs 20%, P ¼ 0.009; 1 vs 9%, P ¼ 0.004; 3 vs 10%, P ¼ 0.007; 1 vs 9%, P ¼ 0.005, respectively); in contrast, T/t, A/T, A/t, b/A/t were higher in flare(s) (8 vs 3%, P ¼ 0.003; 49 vs 34%, P ¼ 0.027; 2 vs 1%, P ¼ 0.004; 0.5 vs 0%, P ¼ 0.001, respectively).

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“…It was previously shown that vitamin D daily supplementation in the diet, as well as calcitriol intraperitoneal administration (IP) three times a week (0.05 μg/mouse) or daily (0.5 μg/kg) can inhibit growth of MCF7 (breast cancer cells) or SKHEP (liver cancer cells) xenograft growth in nude mice (Pourgholami et al, 2000;Swami et al, 2012). In human beings, it was also reported that after subcutaneous administration, calcitriol plasma concentrations reach and maintain peak levels between 2 and 8 hours, returning to the normal physiological range after 48 hours (Smith et al, 1999;Beer et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

et al. 2017

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Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. Objectives: To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Methods: Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Results: Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. Conclusions: Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.Keywords: tumorgraft, breast cancer, calcitriol, proliferation. Modelo de enxerto tumoral ortotópico em camundongos para avaliar os efeitos do calcitriol em câncer de mama ResumoOs efeitos antiproliferativos de calcitriol foram observados em xenotransplantes de linhagens celulares de câncer de mama, entretanto, não foram ainda investigados em enxertos tumorais, consistindo de implantes em animais de amostras de câncer de mama recém-coletadas. Objetivos: Estabelecer modelo de enxerto tumoral, a partir de amostra de câncer de mama recém-coletada e diretamente implantada em camundongos nude, para estudar o efeito do calcitriol. Métodos: Amostras de câncer de mama de 12 pacientes foram implantadas ortotopicamente em camundongos nude. Os animais foram tratados com injeção intratumoral semanal de calcitriol 3 μg/Kg, a qual foi previamente associada com indução de pico sérico de calcitriol dentro do intervalo de nível terapêutico. Resultados: A taxa de sucesso de pega do enxerto foi de 25%. Os enxertos tumorais foram estabelecidos de tumores agressivos com alta taxa de proliferação (HER2 positivo ou grau histológico 3) e as características do tumor original foram preservadas. O calcitriol induziu fortemente a expressão do gene alvo, CYP24A1, indicando que a via genômica da vitamina D está ativa nos enxertos tumorais, entretanto, não se observou diferenças na expressão de marcadores de proliferação e apoptose (incorporação de BrdU, expressão de Ki67, CDKN1A, CDKN1B e BCL2) nestas amostras altamente proliferativas. Conclusões: Os enxertos tumorais parecem ser um modelo promissor para explorar outros esquemas e doses de calcitriol, considerando a heteroge...

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In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3

Cited by 58 publications

References 22 publications

Hepatocellular carcinoma in Txnip-deficient mice

Hepatocellular carcinoma in Txnip-deficient mice

Vitamin D receptor gene polymorphisms and distinct clinical phenotypes of hepatitis B carriers in Taiwan

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

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