Figure 6. EGLN1 deletion or inhibition reduces tumor formation induced by EGLN1-dependent cells.

A. Schematic of tumor formation experiments. Each recipient mouse receives control (sgChr2–1) and EGLN1-KO cells.

B. EGLN1 knockout impairs tumor formation induced by ES2 cells. Control and EGLN1 KO ES2 cells (100,000) were injected subcutaneously in parallel flanks and tumor size was measured. Data is represented as mean ± standard deviation (n=15) and represents two experimental repeats *p<0.01.

C. EGLN1 knockout impairs tumor formation induced by OVISE cells. Control and EGLN1 KO OVISE cells (250,000) were injected subcutaneously in parallel flanks and tumor size was measured. Data is represented as mean ± standard deviation (n=6) *p<0.05.

D. EGLN1 expression levels in the knockout cells correlate with tumor size. RNA was harvested from tumors and expression was quantified using qRT-PCR. Data is represented as the average of four biological replicates and represents two experimental repeats.

E. Microdevice delivery of EGLN1 inhibitors and VHL inhibitors to ovarian tumor with HIF1A expression reduces proliferation. Microdevices were loaded with PEG-formulated compounds and implanted into 1cm² tumors formed from ES2 or from ES2 with HIF1A KO and grown to 1cm². At 48 hours post microdevice implantation tumors are harvested and serially sectioned and stained. The control for drug formulation (PEG Control) has no effect on the proliferation of ES2 tumor cells with or without HIF1A (top). Doxorubicin treatment reduces tumor cell proliferation (top middle). Inhibition of EGLN1 with FG-4592 blocks proliferation of tumor cells, while knockout of HIF1A rescues EGLN1 inhibition (bottom middle). Inhibition of VHL with VH298 blocks proliferation of tumor cells while knockout of HIF1A rescues VHL inhibition. Figure is representative of three independent experiments. Arrow shows area where drug is released. Black line indicates 1mM.