ABSTRACT
This paper showed bioprinted HepG2 tumor tissues used for studying the sonodynamic anticancer activity of chlorine e6 (Ce6). HepG2 cells were printed by using alginate/gelatin/hydroxyethyl cellulose composite biomaterial as bio ink and cell viability was detected with Live-Dead assay and MTT proliferation. The ultrasonic intensities of self-built micro ultrasonic device under different powers were estimated by using the temperature change caused by the conversion of acoustic energy to heat energy. Ce6 of 14.3 and 28.6 μg·mL-1 were acted on two-dimensional cultured and three-dimensional printed HepG2 cells, and the antitumor activity of Ce6 was detected by MTT method with ultrasound intensity of 0.15 W·cm2 for 60 s. The results showed that the activities of bioprinted HepG2 cells were as high as 95%, and tumor microspheres were formed after 7 days of culture. The ultrasound intensity was lower than 3 W·cm2, which belonged to low ultrasound intensity and had no damage to normal hepatocyte LO2 cells. By comparing the antitumor activity of Ce6 on 2D cultured and printed HepG2 cells, it was found that the anticancer activity of Ce6 on bioprinted HepG2 cells was 63.4% lower than that on 2D culture cells, indicating the acoustic drug resistance of three-dimensional tumor model. Bioprinted tumor tissues show the potential in the application of in vitro activity evaluation models for sonodynamic therapy.
ABSTRACT
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.
