Lurbinectedin (PM01183)

Cell experiment:

The MTS assay is used to analyze the effects of each drug. Cells are plated in 96-well plates and treated with PM01183 (0, 0.1, 0.3, 1, 3 nM) . After 48 hours’ incubation, the number of surviving cells is assessed by determining the A490nm of the dissolved formazan product after the addition of MTS for 1 hour. Cell viability is calculated as follows: Aexp group / Acontrol×100[1].

Animal experiment:

Mice: Mice are transplanted with fragments of OVAX1 and OVAX1R tumors, and when tumors reaches a homogeneous palpable size are randomly allocated into the treatment groups: i) Placebo; ii) Lurbinectedin (0.18 mg/kg); iii) Cisplatin (3.5 mg/kg); and iv) Lurbinectedin plus cisplatin (0.18 + 3.5 mg/kg). Drugs are i.v. administered once per week for 3 consecutive weeks (days 0, 7, and 14). Seven days after the final dose (day 21), animals are sacrificed, their ovaries dissected out, and weighed. Representative fragments are either frozen in nitrogen or fixed and then processed for paraffin embedding[3].

References:

[1]. Takahashi R, et al. Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary. PLoS One. 2016 Mar 17;11(3):e0151050.
[2]. Leal JF, et al. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. Br J Pharmacol. 2010 Nov;161(5):1099-110.
[3]. Vidal A, et al. Lurbinectedin (PM01183), a new DNA minor groove binder, inhibits growth of orthotopic primary graft of cisplatin-resistant epithelial ovarian cancer. Clin Cancer Res. 2012 Oct 1;18(19):5399-411.