![]() ![]() PANC1 and Patu8988 cells were seeded into 96-well plates overnight, then exposed to conditions, and treated with reagents as indicated at the indicated time (6, 12, and 24 hours). Cell Viability AssayĬell viability was measured using Cell Counting Kit-8 (CCK-8 Dojindo, #CK04). #Pancrea tabs plus keygen#Propidium iodide (PI) was purchased from KeyGEN BioTECH. BODIPY-C11 (#D2861) was obtained from Invitrogen. H/NS condition was performed in DMEM with 2% FBS and antibiotics (100 units/mL penicillin, 100 mg/mL streptomycin) at 94% N 2, 5% CO 2, and 1% O 2 for the indicated time (6, 12, and 24 hours). Nutrient starvation (NS) condition was performed in DMEM with 2% FBS and antibiotics (100 units/mL penicillin, 100 mg/mL streptomycin). Hypoxic (H) incubation was performed at 94% N 2, 5% CO 2, and 1% O 2. Cells were cultured in high glucose Dulbecco’s modified Eagle medium (DMEM) with 10% fetal bovine serum (FBS ExCell FSP500) and antibiotics (100 units/mL penicillin, 100 mg/mL streptomycin) at 37☌ in an incubator with a humidified atmosphere of 5% CO 2. ![]() Human pancreatic cancer cell lines (BXPC3, SW1990, PANC1, and Patu8988) and mice pancreatic cancer cell line Panc02 were obtained from the Cell Bank of the China Academy of Sciences (Shanghai, China). Silencing of SCD1 in H/NS cultured pancreatic cancer cells enhanced erastin induced ferroptosis in vitro and in vivo, which suggests a potential ferroptosis-based therapeutic strategy for pancreatic cancer. To test this hypothesis, we show that pancreatic cancer cells under H/NS condition are associated with the upregulation of SCD1 expression and ferroptosis inducer resistance. These findings suggested that SCD1 may be involved in H/NS microenvironment-induced ferroptotic cell death resistance in cancer cells. Stearoyl-CoA desaturase 1 (SCD1), a critical regulator of de novo synthesis, catalyzes the desaturation of saturated fatty acids (SFAs) to MUFAs. Monounsaturated fatty acids (MUFAs) block the lipid ROS accumulation on the plasma membrane and further induce the ferroptosis-resistant state. #Pancrea tabs plus free#Polyunsaturated fatty acids (PUFAs) promote free radical generation and lipid peroxide accumulation, which act as a trigger for ferroptosis. Extensive researches show that ferroptosis was tightly related to the FA balance. Under H/NS, cancer cells mostly depended on metabolism reprogramming, such as elevated de novo synthesis of fatty acids (FAs), for the sake of thriving. However, the exact mechanisms were still unclear. Recently, more and more researches demonstrated tumor microenvironment, and energy materials were also critical regulators of ferroptosis. Therefore, it is necessary to investigate the mechanisms underlying the H/NS microenvironment mediating the cancer cell death resistance.įerroptosis, a newly identified type of programmed cell death, is characterized by iron-dependent lipid peroxidation. #Pancrea tabs plus driver#H/NS microenvironment is not only the driver of pancreatic cancer cell growth and metastasis but also inducing cancer cell death resistance, which ultimately results in therapy failure. Introductionĭue to the imbalance of unlimited proliferation of cancer cells and poor supplement of blood vessels, hypoxia and nutrient starvation (H/NS) has been recognized as the most important characteristic of pancreatic carcinoma microenvironment. Taken together, our findings reveal a new role of the H/NS microenvironment against ferroptosis and suggest a potential therapeutic strategy for overcoming ferroptosis resistance in pancreatic cancer cells. Finally, our results demonstrate the synergistic effect of erastin and A939572, a special SCD1 inhibitor, in dictating pancreatic carcinoma subcutaneous ferroptotic death. Moreover, short-hairpin RNA-based knockdown of SCD1 enhanced erastin-induced ferroptosis in vitro under H/NS. ![]() Surprisingly, SCD1 showed a strong correlation with antiferroptosis gene expression. Mechanistically, H/NS induced the upregulation of stearoyl-CoA desaturase 1 (SCD1), which promoted monounsaturated fatty acids (MUFAs) synthesis and protected against lipid peroxidation. Here, we found that H/NS contributed to the pancreatic cancer cell ferroptosis resistance depending on the altered intracellular lipid compositions. However, its role in ferroptosis remains to be classified. Hypoxia and nutrient starvation (H/NS) microenvironment, a notable characteristic of pancreatic carcinoma, plays a critical role in cell death resistance and tumor recurrence. ![]()
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