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Published on: September 19, 2019
Application of microfluidic gradient chip in the analysis of lung cancer chemotherapy resistance
Wang Siyan1, Yue Feng, Zhang Lichuan
1Department of Emergencyt, The Second Hospital Affiliated to Dalian Medical University, 467 Zhongshan Road, Dalian 116023, China.
Abstract:
The major challenge of chemotherapy is the disease resistance for many lung cancer patients. Integrated microfluidic systems offer many desirable characteristics and can be used in cellular biological analysis. This work aimed to study the correlation between the expression of Glucose Regulated Protein-78 (GRP78) and the resistance to anticancer drug VP-16 in human lung squamous carcinoma cell line SK-MES-1 using an integrated microfluidic gradient chip device. We used A23187, a GRP78 inducer, with a gradient concentration in the upstream network of the device to induce the expression of GRP78 in the cells cultured in the downstream before the addition of VP-16. The expression of GRP78 was detected by immunofluorescence, the apoptosis for the cells treated by VP-16 was assessed morphologically by 4',6-diamidino-2-phenylindole (DAPI) staining. The results indicated that the expressions of GRP78 increased greatly for the cells under the induction of A23187 with a dose-depended manner, while the percentage of apoptotic cells decreased significantly after being treated by VP-16. Our results from this study confirmed the role of GRP78 played in the chemotherapy resistance to VP-16 in SK-MES-1 cell line, suggesting that the integrated microfluidic systems may be an unique approach for characterizing the cellular responses.
Insights
Elevated Glucose Regulated Protein-78 (GRP78) expression correlates with reduced VP-16 chemotherapy resistance in lung cancer cells. Microfluidic systems effectively demonstrated this link, offering insights into overcoming drug resistance.
Area of Science:
- Biochemistry
- Cell Biology
- Biomedical Engineering
Background:
- Chemotherapy resistance is a significant challenge in treating lung cancer.
- Integrated microfluidic systems provide advanced platforms for cellular analysis.
- Glucose Regulated Protein-78 (GRP78) is implicated in cellular stress responses and drug resistance.
Purpose of the Study:
- To investigate the correlation between Glucose Regulated Protein-78 (GRP78) expression and resistance to the anticancer drug VP-16.
- To utilize an integrated microfluidic gradient chip for inducing and assessing GRP78 expression.
- To evaluate the impact of GRP78 induction on VP-16-induced apoptosis in lung cancer cells.
Main Methods:
- Employing an integrated microfluidic gradient chip to deliver varying concentrations of A23187, a GRP78 inducer.
- Culturing human lung squamous carcinoma cells (SK-MES-1) on the microfluidic device.
- Detecting GRP78 expression via immunofluorescence and assessing apoptosis using DAPI staining after VP-16 treatment.
Main Results:
- A23187 induction led to a dose-dependent increase in GRP78 expression in SK-MES-1 cells.
- Elevated GRP78 expression was associated with a significant decrease in VP-16-induced apoptosis.
- The study confirmed GRP78's role in mediating VP-16 resistance in this lung cancer cell line.
Conclusions:
- GRP78 expression plays a crucial role in conferring resistance to VP-16 chemotherapy in SK-MES-1 lung cancer cells.
- Integrated microfluidic systems are effective tools for studying cellular responses to drug treatments.
- Targeting GRP78 may represent a potential strategy to overcome chemotherapy resistance in lung cancer.
