RESUMO
BACKGROUND: According to modern literature, osteopontin (OPN) and osteonectin (ON) are involved not only in the formation of the aggressive phenotype of malignantly transformed cells, but also in the realization of cytotoxic effects of some antitumor drugs. AIM: To study the changes of the expression of OPN and ON and their mRNAs (SPP1 and SPARC) upon exposure to doxorubicin (Dox) in breast cancer (BCa) and prostate cancer (PCa) cell lines with different sensitivity to Dox. MATERIALS AND METHODS: Cell lines of BCa (MCF-7 and MDA-MB-231) and PCa (LNCaP and DU-145) were cultured in the presence of Dox at IC30 concentrations for 24 h. OPN and ON levels were assessed by immunocytochemical (ICH) and Western blot analysis. SPP1 and SPARC mRNA levels were assessed by quantitative PCR. RESULTS: Dox treatment resulted in the significant decrease in the expression of both OPN and ON in MCF-7 and LNCaP cells. Similarly, Dox treatment downregulated both SPP1 and SPARC in MDA-MB-231 and DU-145 cells. Dox did not affect ON expression in MDA-MB-231 and DU-145 cells although the significant decrease in the level of SPARC mRNA has been evident. In contrast, no significant differences in SPP1 and SPARC mRNA levels were detected in LNCaP cells. CONCLUSION: The changes in the expression of OPN and ON proteins and their corresponding genes in BCa and PCa cells may be related to the intrinsic mechanisms of Dox effects in cells differing by malignant phenotype and Dox sensitivity.
Assuntos
Antineoplásicos , Neoplasias da Próstata , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Humanos , Masculino , Osteonectina/genética , Osteopontina/genética , Osteopontina/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , RNA MensageiroRESUMO
AIM: To evaluate antitumor effect of plant polyphenol extracts from green tea, red wine lees and/or lemon peel alone and in combination with antitumor drugs on the growth of different transplanted tumors in experimental animals. MATERIALS AND METHODS: Green tea extract (GTE) was prepared from green tea infusion. GTE-based composites of red wine (GTRW), lemon peel (GTRWL) and/or NanoGTE as well as corresponding nanocomposites were prepared. The total polyphenolics of the different GTE-based extracts ranged from 18.0% to 21.3%. The effects of GTE-based extracts were studied in sarcoma 180, Ehrlich carcinoma, B16 melanoma, Ca755 mammary carcinoma, P388 leukemia, L1210 leukemia, and Guerin carcinoma (original, cisplatin-resistant and doxorubicin-resistant variants). The extracts were administered as 0.1% solution in drinking water (0.6-1.0 mg by total polyphenolics per mouse per day and 4.0-6.3 mg per rat per day). RESULTS: Tumor growth inhibition (TGI) in mice treated with NanoGTE, cisplatin or cisplatin + NanoGTE was 27%, 55% and 78%, respectively, in Sarcoma 180%, 21%, 45% and 59%, respectively, in Ehrlich carcinoma; and 8%, 13% and 38%, respectively in B16 melanoma. Composites of NanoGTE, red wine, and lemon peel (NanoGTRWL) enhanced the antitumor effects of cyclophosphamide in mice with Ca755 mammary carcinoma. The treatment with combination of NanoGTE and inhibitors of polyamines (PA) synthesis (DFMO + MGBG) resulted in significant TGI of P388 leukemia (up to 71%) and L1210 leukemia. In rats transplanted with Guerin carcinoma (parental strain), treatment with GTRW or GTE alone resulted in 25-28% TGI vs. 55-68% TGI in cisplatin-treated animals. The inhibition observed in the case of combination of GTE or GTRW with cisplatin was additive giving 81-88% TGI. Similar effects were observed when combinations of the cytostatics with GTE (or NanoGTE) were tested against cisplatin- or doxorubicin-resistant Guerin carcinoma. Moreover, the plant extracts lowered side toxicity of the drugs. Treatment with GTE, NanoGTE, and NanoGTRW decreased the levels of malondialdehyde in heart, kidney and liver tissue of experimental animals, as well as the levels of urea and creatinine in blood serum, increased erythrocyte and platelet counts, hemoglobin content, and decreased leucocyte counts. CONCLUSION: The obtained data indicate the prospects for further development of GTE and corresponding nanocomposites as auxiliary agents in cancer chemotherapy.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Citrus/química , Neoplasias Experimentais/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Chá/química , Animais , Antineoplásicos/química , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ratos , VinhoAssuntos
Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Extratos Vegetais/farmacologia , Poliaminas/metabolismo , Polifenóis/farmacologia , Chá , Animais , Proliferação de Células/efeitos dos fármacos , Guanidinas/farmacologia , Humanos , Neoplasias Experimentais/metabolismo , FitoterapiaRESUMO
The comparative analysis of the data on the expression of the same modulating protein MX, obtained on the same biological materials by Western blotting and surface plasmone resonance tests was shown to provide in most cases a semiquantitative opinion as to modulation of MX affinity to its specific target (effector X protein) under the experimental action of F. This is doubtlessly to offer additional possibilities for the prediction and differential diagnosis of a number of diseases, including cancer.
Assuntos
Carcinoma 256 de Walker/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Western Blotting , Extratos Celulares , Núcleo Celular/metabolismo , Ligação Proteica , Ressonância de Plasmônio de SuperfícieRESUMO
EPH gestosis is one from most serious complications stepping out in pregnancy. Reason of occurrence gestosis to this times did not become explained in spite of existences of many theories on theme etiopathogenesis. Stoutness weighty pregnant women in opinion many authors is factor predestinating to occurrences gestosis. Material investigative determined 2 groups: one group--43 healthy weighty pregnant women, and second group--18 pregnant women with gestosis. In each groups investigated one qualified average age of women, MAP, and body mass index (BMI). Our investigations had to answer on following questions: 1. has stoutness influence on course of pregnancy and of childbirth state of new-born child? 2. has stoutness influence on height of arterial pressure in pregnancy? The results shown one ascertained correlation between MAP and BMI in group of weighty pregnant women with EPH gestosis.