Abstract
Objective: To investigate whether low-dose fractionated radiation (LDFRT) could enhance gemcitabine sensitivity in drug-resistant human pancreatic cancer SW1900/GZ cell, and to further explore the underlying mechanism. Methods: Gemcitabine-resistant human pancreatic cancer SW1900 cell line (SW1900/GZ) was induced by high concentration gemcitabine intermittent shock in vitro. The cell counting kit 8 (CCK8) was used to determine SW1900/GZ cell lines. SW1900/GZ cells were divided into six groups as follows: control, LDFRT, high dose radiation (HDRT), gemcitabine (GEM), low dose fractional radiation plus gemcitabine (LDFRT+ GEM) and high dose radiation plus gemcitabine (HDRT+ GEM) groups. The rate of apoptosis was determined by flow cytometry (FCM). Protein levels of multidrug resistance gene (MDR) and multidrug resistance-related protein gene (MRP) were examined by Western blotting. Results: The results of CCK8 test showed that the half-maximal inhibitory concentration (IC50) of non-drug-resistant cell line SW1900 and drug-resistant cell line SW1990/GZ were 230.4ng/ml and 856.6ug/ml respectively. The IC50 of SW1990/GZ was 3700 times more than the former. LDFRT significantly promoted apoptosis in SW1900 cells. Moreover, in the LDFRT group, protein levels of MDR and MRP were markedly decreased. Conclusion: This study established an effective gemcitabine-resistant cell line SW1900 of human pancreatic cancer (SW1900/GZ cell line). LDFRT sensitizes resistant SW1900/GZ pancreatic cancer cell to gemcitabine through down-regulation the expression of MDR and MPR proteins.
Highlights
Pancreatic cancer is the sixth leading cause of cancer-associated deaths in China with about 90,100 new cases and 79,400 deaths by the end of 2015 [1, 2]
In order to explore the enhancement of chemosensitivity by low dose fractionated radiation (LDFRT), we chose the concentration of GEM of 200 ug/ml to detect apoptosis by flow cytometry (FCM)
The results showed that the expression of multidrug resistance gene (MDR) and multidrug resistance-related protein gene (MRP) in the cell line SW1990/GZ was significantly up-regulated compared with the nondrug-resistant cell line, as shown in (Figure 3a)
Summary
Pancreatic cancer is the sixth leading cause of cancer-associated deaths in China with about 90,100 new cases and 79,400 deaths by the end of 2015 [1, 2]. In the United States, it is estimated that pancreatic cancer will become the second leading cause of cancer-related deaths by 2030 [3]. Cancer of the pancreas remains one of the most deadly common cancer types: the Mortality/Incidence ratio is 98% [4]. Year survival rate is about 6% with a range from 2-9%, partly reflecting varying data quality worldwide. The survival rates vary very small between developed and developing countries [5]. Chemotherapy remains the main treatment for most patients with pancreatic cancer to alleviate the symptom and prolong the survival [2]
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