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Fig. 1 | BMC Cancer

Fig. 1

From: Autophagy modulating therapeutics inhibit ovarian cancer colony generation by polyploid giant cancer cells (PGCCs)

Fig. 1

Polyploid Giant Cancer Cell (PGCC) life cycle and experimental setup for CAOV3 and OVCAR3 PGCC induction and subsequent progeny generation. A PGCC life cycle depicting a diploid cancer cell undergoing chemotherapy-induced polyploidization followed by neosis – the generation of diploid progeny through depolyploidization. B Timeline for assessing the effect of the autophagy modulators hydroxychloroquine (HCQ), nelfinavir mesylate (NFV), and rapamycin (Rapa) on carboplatin- (CPt) or docetaxel- (DTx) induced PGCC formation and subsequent progeny generation. CAOV3 or OVCAR3 cells were seeded on day 0, treated with chemotherapy drugs CPt or DTx from day 1 through day 4, allowed to recover for three days. To assess the effect of the autophagy modulators on PGCC formation, cells were treated with HCQ, NFV, or Rapa concurrently with CPt or DTx, then fixed, stained, and imaged on day 7 as described in Methods. C To assess the effect of the autophagy modulators on PGCC progeny development, cells were treated with CPt or DTx from day 1 through day 4 and allowed to recover from day 4 – day 7 as above, but then PGCCs were separated based on cell size and re-plated, allowed to adhere overnight, then treated with HCQ, NFV, or Rapa on day 8 through day 14 – a time during which PGCCs form progeny. Finally, PGCC progeny were fixed, stained with crystal violet, imaged, and quantified as described in Methods. D Clinically available autophagy drugs used in this study are briefly diagrammed for their mechanisms in terms of proteotoxic stress and modulation of functional autophagy

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