Cell lines

EC109 and EC9706 cell lines

Preparation Method

Both cell lines were cultured in RPMI 1640 supplemented with 10% FBS at 37℃ in a 5% CO2 humidified incubator. Cells were starved for 24 h in medium containing 0.1% FBS prior to treatment.

Reaction Conditions

PX-478 was added to the cultures to a final concentration of 20 umol/L after serum starvation overnight.

Applications

PX-478 could inhibit normoxic and hypoxia-induced HIF-1α expression as well as COX-2 and PD-L1 expression in vitro at a dose of 20 μM in EC9706 and EC109 cells. Targeted HIF-1α can effectively reduce their expression.

Animal models

6-week-old female BALB/c nude mice, 18 ± 2 g, SPF grade

Preparation Method

EC109 cells were re-suspended in PBS at 10⁷/mL. A total of 12 BABL/c nude female mice were used. Mice were injected with EC109 cells in the right flank area to establish the tumor xenograft. The 12 tumor-bearing mice in each group were randomly divided into the control group and the PX-478 groups. All the drugs were delivered via p.o. gavage administration.

Dosage form

30 mg/kg every other day

Applications

PX-478 shows a wide effect on tumor development, such as suppressing proliferation, promoting cells apoptosis, inhibiting EMT process and arresting cell cycle. In vivo mouse xenograft models showed the inhibitory effect on tumor growth. In addition, it can reduce COX-2 and PD-L1 expression.

• Toxicol Appl Pharm (2022): 115910. PMID:35134435
• J Mater Chem B (2022). PMID:35971918

PX-478 is a selective inhibitor that suppresses constitutive and hypoxia-induced HIF-1α levels. PX-478 inhibits HIF-1α at multiple levels including inhibition of HIF-1α translation and reduction in HIF-1α mRNA levels.^[1]PX-478 also has been shown antitumor activity against several aggressive human tumor xenografts.^[2]

In vitro and in vivo study demonstrated that PX-478 could inhibit normoxic and hypoxia-induced HIF-1α expression as well as inflammatory molecule COX-2 and immunosuppressive molecule PD-L1 expression. Therefore, PX-478 shows a wide effect on tumor development, such as suppressing proliferation, promoting cells apoptosis, inhibiting EMT process and arresting cell cycle. In vivo experiment indicated the inhibitory effect of PX-478 on tumor growth.^[1]

References:
[1].Zhu Y, et al. Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo. Am J Cancer Res. 2017 May 1;7(5):1198-1212.
[2].Palayoor ST, et al. PX-478, an inhibitor of hypoxia-inducible factor-1alpha, enhances radiosensitivity of prostate carcinoma cells. Int J Cancer. 2008 Nov 15;123(10):2430-7.