title: New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer.
abstract: Small cell lung cancer (SCLC) remains one of the most aggressive tumors with a poor prognosis. The clinical outcome of SCLC patients has reached its plateau with the existing standard treatment and thus new therapies are urgently required. Accumulating evidences have indicated that doxycycline, a commonly used antibiotic, has antitumor activity against several malignancies. However, whether doxycycline has antitumor activity in SCLC and its underlying mechanisms remain unclear. Our investigation demonstrated that doxycycline could significantly inhibit the proliferation and colony formulation of SCLC cells (p<0.05). Furthermore, both Hoechst 33258 dye staining and TUNEL assays indicated that doxycycline could induce remarkable apoptosis of H446 cells in a concentration-dependent manner. RT-PCR and western blot assays proved that apoptosis induction effect of doxycycline was achieved via inducing the expression of caspase-3 and bax, as well as attenuating the expression of survivin and bcl-2. Moreover, the wound healing assay and Transwell assay indicated that doxycycline could significantly suppress the migration and invasion of H446 cells in a concentration-dependent manner (p<0.05). ELISA assay proved that the inhibitory effect of doxycycline on the migration and invasion of H446 cells was achieved via decreasing the secretion of MMP-2, MMP-9 and VEGF, as well as increasing the secretion of TIMP-2. Taken together, doxycycline dose-dependently suppressed the proliferation, colony formulation, migration and invasion of SCLC cells, as well as induced apoptosis. These findings encourage further investigations on the potential of doxycycline as a candidate drug for the treatment of SCLC.
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Sheng-Qi
authors: SQ
authors: Wang
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Bo-Xin
authors: BX
authors: Zhao
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Yuan
authors: Y
authors: Liu
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Ya-Tian
authors: YT
authors: Wang
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Qian-Ying
authors: QY
authors: Liang
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Yun
authors: Y
authors: Cai
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Yun-Qi
authors: YQ
authors: Zhang
authors: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, Gansu 750004, P.R. China.
authors: Jiang-Hong
authors: JH
authors: Yang
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Zhi-Hua
authors: ZH
authors: Song
authors: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Guo-Feng
authors: GF
authors: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004318:Doxycycline / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D004318:Doxycycline