title: Ultrasound-mediated destruction of oxygen and paclitaxel loaded lipid microbubbles for combination therapy in hypoxic ovarian cancer cells.
abstract: We synthesized oxygen and paclitaxel (PTX) loaded lipid microbubbles (OPLMBs) for ultrasound mediated combination therapy in hypoxic ovarian cancer cells. Our experiments successfully demonstrated that ultrasound induced OPLMBs destruction significantly enhanced the local oxygen release. We also demonstrated that OPLMBs in combination with ultrasound (300 kHz, 0.5 W/cm(2), 15s) yielded anti-proliferative activities of 52.8 ± 2.75% and cell apoptosis ratio of 35.25 ± 0.17% in hypoxic cells at 24h after the treatment, superior to other treatment groups such as PTX only and PTX-loaded MBs (PLMBs) with or without ultrasound mediation. RT-PCR and Western blot tests further confirmed the reduced expression of HIF-1α and MDR-1/P-gp after ultrasound mediation of OPLMBs. Our experiment suggests that ultrasound mediation of oxygen and drug-loaded MBs may be a useful method to overcome chemoresistance in the hypoxic ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Shenyin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ronald X
authors.initials: RX
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: shfch2005@163.com.
authors.forename: Shufang
authors.initials: S
authors.lastname: Chang
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D045423:Microbubbles; D010051:Ovarian Neoplasms / Q000473:pathology*; D010100:Oxygen / Q000737:chemistry* / Q000494:pharmacology; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D000069453:Ultrasonic Waves
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010714:Phosphatidylethanolamines; D015060:1,2-Dipalmitoylphosphatidylcholine; C483858:phosphatidylethanolamine; D017239:Paclitaxel; D010100:Oxygen
keywords: Drug delivery; Fluorescence; Microbubbles; Oxygen; Perfluorocarbon; Ultrasound