Background
Pirarubicin is an anthracycline that has anticancer activity.1 It interacts with topoisomerase II to inhibit DNA replication. Pirarubicin inhibits the growth of human HeLa and C33A cervical, as well as T-24 bladder cancer cells (IC50s = 29, 52, and 36 ng/ml, respectively).2 It inhibits the growth of human Huh7 and MHCC97H liver cancer cells (IC50s = 0.159 and 0.374 μM, respectively).3 Pirarubicin also inhibits the growth of M5076 mouse ovarian cancer cells in vitro (IC50 = 0.366 μM) and in vivo in a mouse allograft model when administered at a dose of 2 mg/kg for four days.4
1.Monneret, C.Recent developments in the field of antitumour anthracyclinesEur. J. Med. Chem.36(6)483-493(2001)
2.Tsuchiya, K.S., Ishii, T., Ikeno, S., et al.Inhibition of anchorage-independent growth of tumor cells by IT-62-B, a new anthracyclineJ. Antibiot. (Tokyo)50(10)853-859(1997)
3.Huang, H., Chen, T., Zhou, Y., et al.RIPK1 inhibition enhances pirarubicin cytotoxic efficacy through AKT-P21-dependent pathway in hepatocellular carcinomaInt. J. Med. Sci.15(14)1648-1657(2018)
4.Sugiyama, T., Sadzuka, Y., Nagasawa, K., et al.Membrane transport and antitumor activity of pirarubicin, and comparison with those of doxorubicinJpn. J. Cancer Res.90(7)775-780(1999)
Protocol
Cell experiment: | MTS is used to analyze cell survival. Briefly, cells are plated in 96-well plates in triplicate at 2 × 103 cells per well and cultured in growth medium. Then cells are treated with pirarubicin at different concentrations (2.5 μg/mL, 5 μg/mL, 10 μg/mL) for 24 h. MTS reagent (5 mg/mL) is added and incubated at 37°C for 4 h. The absorbance is monitored at 490 nm using a microplate reader[3]. |
Animal experiment: | An acute cardiac toxicity model is established by a single dose of 18 mg/kg pirarubicin through the caudal vein injection. Thirty-six rats are randomized equally to six groups: normal control, cardiac injury (THP) model, dexrazoxane (180 mg/kg), low-dose rutin (25 mg/kg), middle-dose rutin (50 mg/kg), and high-dose rutin (100 mg/kg). Rats in the rutin-treated group are administered different doses of rutin and CMC-Na for 7 days by gavage and a single dose of 18 mg/kg pirarubicin through caudal vein injection. Rats in the dexrazoxane-treated group receive sodium carboxymethylcellulose (CMC-Na) by gavage for six days. 40 mg/kg dexrazoxane is then administered to rats by intraperitoneal injection and 18 mg/kg pirarubicin is administered by caudal vein injection on day 7. Rats in the THP model group receive CMC-Na by gavage for seven days, followed by pirarubicin 18 mg/kg through the caudal vein injection on day 7. Rats in the normal control group receive CMC-Na by gavage for seven days, followed by saline through caudal vein injection on day 7[4]. |
参考文献: [1]. Takigawa N, et al. Cytotoxic effect of topoisomerase II inhibitors against adriamycin- and etoposide-resistant small cell lung cancer sublines. Gan To Kagaku Ryoho. 1993 May;20(7):929-35.
[2]. Nagai K, et al. Relationships between the in vitro cytotoxicity and transport characteristics of pirarubicin and doxorubicin in M5076 ovarian sarcoma cells, and comparison with those in Ehrlich ascites carcinoma cells. Cancer Chemother Pharmacol. 2002 Mar;49(3):244-50. Epub 2002 Jan 8.
[3]. Li K, et al. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells. Biochem Biophys Res Commun. 2015 May 1;460(2):380-5.
[4]. Wang YD, et al. Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity. J Asian Nat Prod Res. 2017 Oct 27:1-13. |
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