A microfluidic system to study the cytotoxic effect of drugs: the combined effect of celecoxib and 5-fluorouracil on normal and cancer cells

Abstract

We have investigated the response of normal and cancer cells to exposure a combination of celecoxib (Celbx) and 5-fluorouracil (5-FU) using a lab-on-a-chip microfluidic device. Specifically, we have tested the cytotoxic effect of Celbx on normal mouse embryo cells (Balb/c 3T3) and human lung carcinoma cells (A549). The single drugs or their combinations were adjusted to five different concentrations using a concentration gradient generator (CGG) in a single step. The results suggest that Celbx can enhanced the anticancer activity of 5-FU by stronger inhibition of cancer cell growth. We also show that the A549 cancer cells are more sensitive to Celbx than the Balb/c 3T3 normal cells. The results obtained with the microfluidic system were compared to those obtained with a macroscale in vitro cell culture method. In our opinion, the microfluidic system represents a unique approach for an evaluation of cellular response to multidrug exposure that also is more simple than respective microwell plate assays. Figureᅟ

Keywords: 5-fluorouracil; Celecoxib; Chemotherapy resistance; Lab-on-a-chip; Microfluidic gradient system; Multidrug tests.

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Fig. 1

a The microfluidic system integrated with concentration gradient generator (CGG) consists of PDMS and glass. b Microchambers with Balb/c 3T3 and A549 cells cultured for 24 h

Fig. 2

Effects of celecoxib (Celbx), 5-fluorouracil (5-FU) or their combination on viability of A549 in microfluidic system and 96-well plates after 24 and 48 h. Data shown presents averages of four independent experiments. Asterisks indicate P < 0.05

Fig. 3

Effects of celecoxib (Celbx), 5-fluorouracil (5-FU) or their combination on viability of Balb/c 3T3 cells in microfluidic system and 96-well plates after 24 and 48 h. Data shown presents averages of four independent experiments. Asterisks indicate P < 0.05