Reversal of cisplatin resistance in non-small cell lung cancer stem cells by Taxus chinensis var.

Drug resistance in cells is a major impedance to successful treatment of lung cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune function. In this study, T. chinensis var.-induced cell death was analyzed in lung cancer cells (H460) enriched for stem cell growth in a defined serum-free medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123) expression by flow cytometry, and used as a standard functional indicator of MDR. The molecular basis of T. chinensis var.-mediated drug resistance was established by real-time PCR analysis of ABCC1, ABCB1, and lung resistance-related protein (LRP) mRNA, and western blot analysis of MRP1, MDR1, and LRP. Our results revealed that stem cells treated with higher doses of T. chinensis var. showed significantly lower growth inhibition rates than did H460 cells (P < 0.05). The growth of stem and H460 cells treated with a combination of T. chinensis var. and cisplatin was also significantly inhibited (P < 0.05). Rh-123 was significantly accumulated in the intracellular region and showed delayed efflux in stem cells treated with T. chinensis var. (P < 0.05), compared to those treated with verapamil. T. chinensis var.-treated stem cells showed significant downregulation of the ABCC1, ABCB1, and LRP mRNA and MRP1, MDR1, and LRP (P < 0.05) compared to H460 cells. Thus, T. chinensis var.-mediated downregulation of MRP1, MDR1, and LRP might contribute to the reversal of drug resistance in non-small cell lung cancer stem cells.

The role of cellular trace elements in oral carcinogenesis induced by 4-nitroquinoline 1-oxide(4NQO).

The aim of this study was to define the changes of cellular trace element concentration during the carcinogenesis process of Wistar rat palatine mucosa squamous epithelial cell induced by 4-nitroquinoline-1-oxide (4NQO). 4NQO was painted three times weekly for nineteen weeks on the palatine mucosae of 28 Wistar rats. Histologically normal, precancerous and squamous epithelial cell carcinoma tissues were obtained, and were studied by electron probe X-ray microanalysis. The measured elements were copper (Cu), zinc (Zn), selenium (Se), and molybdenum (Mo). The results were that both copper and zinc in the cellular nucleus and cytoplasm of the squamous epithelial carcinoma cells were significantly decreased. The concentration of cytoplasmic molybdenum significantly decreased in precancerous cells and significantly increased in squamous epithelial carcinoma cells. Minor changes in the concentration of selenium were observed in the process of normal to precancerous and then to cancerous cells. Cu/Zn increased in squamous epithelial carcinoma cells and Cu/Se and Zn/Se decreased in squamous epithelial carcinoma cells. These results suggest that the changes in intracellular copper, zinc, molybdenum are distinctly related to experimental oral carcinogenesis.

[The electron probe microanalysis on oral precancer treated by garlic].

OBJECTIVE: To evaluate the effect of 4 kinds of trace elements on experimental oral precancer treated by garlic. METHODS: The palatal mucosae of 42 Wistar rats were painted with 0.5% of 4-nitroquinololine-1-oxide(4NQO) three times weekly for 7 weeks by coating method. Then the animals were divided randomly into two groups. The treatment group was treated three times weekly with garlic solution at the posterior hard palatal mucosae by coating method, and in the control group, the vehicle-distilled water was used instead of garlic solution. At the 5th and 8th weeks of the treatment and the 7th week after the treatment was stopped, some animals were killed. The palatal epithelial cells were prepared and surveyed by electron probe microanalysis. RESULTS: During the treating period, garlic improved the levels of epithelial cells' nuclei copper, selenium, molybdenum and extranuclei selenium, molybdenum(P < 0.01), but it decreased the contents of epithelial cells' extranuclei copper and extra- and intranuclei zinc(P < 0.01). CONCLUSIONS: Garlic can treat the oral precancer by improving the levels of epithelial cells' nuclei copper, selenium, and molybdenum and extranuclei selenium and molybdenum.

[Study on trace elements in epithelial cells during oral carcinogenesis prevented by garlic].

Sixty-two Wistar rats were divided randomly into two groups, thirty-one for each group. The posterior hard palatal mucosae of all animals were painted thrice weekly with 0.5% 4-nitroquinoline 1-oxide(dissolved in dimethyl sulfoxide). Before that, the garlic injection solution and the distilled water were painted at the same place of the experimental and control group animals, respectively. All animals were killed in turn from the beginning of the experiment at random at the 10th, 13th, and 19th week. Then, trace elements of intranuclear and cytoplasm of epithelial cells or cancer cells at the mentioned weeks were surveyed by electron probe microanalysis. The results were that garlic decreased the levels of intranuclear and cytoplasm copper(P < 0.05); the levels of intranuclear and cytoplasm selenium at the 10th week and the 13th week(P < 0.05) and those of zinc at the 19th week (P < 0.01) increased. So, garlic inhibits oral carcinogenesis by changing concentrations of intranuclear and cytoplasm trace elements that is copper, zinc, selenium, and the ratio of the three elements.