Laboratory Center for Diagnostics, Dalian Medical University, Dalian, 116023, Liaoning, China.

Microchip-based systems have many desirable characteristics and can be used in much cellular biochemical analysis. Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, has a critical role in chemotherapy resistance of some cancers. This work aimed at analyzing the correlation between the expression of GRP78 and an anticancer drug, topoisomerase II inhibitor-VP-16, in human lung cancer cell line NCI-H460 using this microchip-based system. The cells were cultured on a PDMS chip, the expression of GRP78 at both protein and mRNA levels for the cells under the condition with or without the induction of A23187 were assayed by immunofluorescence and chip electrophoresis, respectively. Then the cells were treated by VP-16, percentages of apoptosis and the cycle distributions of the cells were detected by flow cytometry. The cells cultured on the PDMS attached and spread well to micro-channels with high viability. Compared with the non-induced cells, the expression of GRP78 at both protein and mRNA levels for the A23187-induced cells were increased greatly. After treatment by VP-16, the percentage of apoptotic cells decreased nearly threefold for the A23187-induced cells in contrast to the non-induced cells (13.15 +/- 3.84% versus 34.03 +/- 11.45%), and the cells distributed in S phase reduced dramatically (11.96 +/- 1.27% versus 20.76 +/- 3.05%) whereas in G(1) phase increased greatly (74.16 +/- 0.95% versus 57.06 +/- 4%). GRP78 is correlated to the resistance to VP-16 in human lung cancer cell line. The microchip-based system has the potential application and feasibility for cell culture and its functional research.

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aDepartment of Genetics, Peking Union Medical College bReproductive and Genetic Center of National Research Institute for Family Planning cWHO Collaborative Center for Research in Human Reproduction dDepartment of Laboratory Animal Science, Peking University, Beijing eNorth China Coal Medical College, Tangshan, China.

In our study we use nordihydroguaiaretic acid (NDGA), the naturally occurring lignan, to investigate whether it plays a role in the prevention and treatment of cancer by epigenetic modifications. The growth inhibitory effect of NDGA on human breast cancer cell lines was determined using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay). It substantially inhibited the growth of human breast cancer cell lines SKBR3 and MDA-MB-435 with an estimated IC50 of 31.09+/-1.6 and 38.8+/-2.1 mumol/l respectively, after 4 days incubation with different NDGA concentrations. The in-vivo anticancer activity of NDGA was evaluated by calculating the tumor growth inhibition value. NDGA substantially inhibited the growth of human breast carcinoma cells in both animal and cell-based models. We also found that a single treatment with NDGA reactivates methylation-silenced E-cadherin gene in vitro and in vivo, suggesting an intriguing concept that lignans may act as natural effective epigenetic modifiers in the prevention and treatment of cancer.

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aDepartment of Genetics, Peking Union Medical College bReproductive and Genetic Center of National Research Institute for Family Planning cWHO Collaborative Center for Research in Human Reproduction dDepartment of Laboratory Animal Science, Peking University, Beijing eNorth China Coal Medical College, Tangshan, China.

In our study we use nordihydroguaiaretic acid (NDGA), the naturally occurring lignan, to investigate whether it plays a role in the prevention and treatment of cancer by epigenetic modifications. The growth inhibitory effect of NDGA on human breast cancer cell lines was determined using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay). It substantially inhibited the growth of human breast cancer cell lines SKBR3 and MDA-MB-435 with an estimated IC50 of 31.09+/-1.6 and 38.8+/-2.1 mumol/l respectively, after 4 days incubation with different NDGA concentrations. The in-vivo anticancer activity of NDGA was evaluated by calculating the tumor growth inhibition value. NDGA substantially inhibited the growth of human breast carcinoma cells in both animal and cell-based models. We also found that a single treatment with NDGA reactivates methylation-silenced E-cadherin gene in vitro and in vivo, suggesting an intriguing concept that lignans may act as natural effective epigenetic modifiers in the prevention and treatment of cancer.

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