Kannen Hiroki, Nomura Shusei, Hazama Hisanao, Kaneda Yasufumi, Fujino Tatsuya, Awazu Kunio
Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Mass Spectrom (Tokyo). 2020;9(1):A0091. doi: 10.5702/massspectrometry.A0091. Epub 2020 Dec 4.
Combined therapy using photodynamic therapy (PDT) and chemotherapy has been proposed for anticancer-drug-resistant cancer cells. To evaluate the efficacy of such a combined therapy, the uptakes of an anticancer drug and a photosensitizer in cancer cells must be assessed. Mass spectrometry using matrix-assisted laser desorption/ionization can detect multiple drugs simultaneously. Human prostate cancer cells PC-3 or docetaxel-resistant cancer cells PC-3-DR were incubated in a serum-free medium containing a photosensitizer, protoporphyrin IX (PpIX), and an anticancer drug, docetaxel. A zeolite matrix was created by mixing 6-aza-2-thiothymine and NaY5.6 zeolite, and dissolving in water with 50% acetone. Ions were obtained with a time-of-flight mass spectrometer using a Nd:YAG laser at a wavelength of 355 nm. The cell morphology was preserved by washing the cells with ammonium acetate and drying in a vacuum after drug administration. Protonated PpIX (/ 563.3) and the sodium adduct ion of docetaxel (/ 829.9) were obtained from PC-3 cells simultaneously using the zeolite matrix. On the other hand, PpIX was detected but ions originating from docetaxel were not detected from PC-3-DR cells. The result indicated the efficacy of PDT for docetaxel-resistant cancer cells.
已提出使用光动力疗法(PDT)和化疗的联合疗法来治疗对抗癌药耐药的癌细胞。为了评估这种联合疗法的疗效,必须评估癌细胞中抗癌药物和光敏剂的摄取情况。使用基质辅助激光解吸/电离的质谱分析可以同时检测多种药物。将人前列腺癌细胞PC-3或多西他赛耐药癌细胞PC-3-DR在含有光敏剂原卟啉IX(PpIX)和抗癌药物多西他赛的无血清培养基中孵育。通过将6-氮杂-2-硫代胸腺嘧啶与NaY5.6沸石混合,并溶解在含50%丙酮的水中来制备沸石基质。使用波长为355 nm的Nd:YAG激光,通过飞行时间质谱仪获得离子。给药后,用醋酸铵洗涤细胞并真空干燥,从而保存细胞形态。使用沸石基质同时从PC-3细胞中获得质子化的PpIX(/ 563.3)和多西他赛的钠加合离子(/ 829.9)。另一方面,从PC-3-DR细胞中检测到了PpIX,但未检测到源自多西他赛的离子。该结果表明了光动力疗法对多西他赛耐药癌细胞的疗效。