Pei-Chia Chan

Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA

Cofilin-1, a non-muscle isoform of actin regulatory protein that belongs to the actin-depolymerizing factor (ADF)/cofilin family is known to affect cancer development. Previously, we found that over-expression of cofilin-1 suppressed the growth and invasion of human non-small cell lung cancer (NSCLC) cells in vitro. In this study, we further investigated whether over-expression of cofilin-1 can suppress tumor growth in vivo, and performed a microRNA array analysis to better understand whether specific microRNA would be involved in this event. The results showed that over-expression of cofilin-1 suppressed NSCLC tumor growth using the xenograft tumor model with the non-invasive reporter gene imaging modalities. Additionally, cell motility and invasion were significantly suppressed by over-expressed cofilin-1, and down-regulation of matrix metalloproteinase (MMPs) -1 and -3 was concomitantly detected. According to the microRNA array analysis, the let-7 family, particularly let-7b and let-7e, were apparently up-regulated among 248 microRNAs that were affected after over-expression of cofilin-1 up to 7 days. Knockdown of let-7b or let-7e using chemical locked nucleic acid (LNA) could recover the growth rate and the invasion of cofilin-1 over-expressing cells. Next, the expression of c-myc, LIN28 and Twist-1 proteins known to regulate let-7 were analyzed in cofilin-1 over-expressing cells, and Twist-1 was significantly suppressed under this condition. Up-regulation of let-7 microRNA by over-expressed cofilin-1 could be eliminated by co-transfected Twist-1 cDNA. Taken together, current data suggest that let-7 microRNA would be involved in over-expression of cofilin-1 mediated tumor suppression in vitro and in vivo.

Pulsed-focused ultrasound enhances boron drug accumulation in a human head and neck cancer xenograft-bearing mouse model.

PurposeThis study aims to demonstrate that pulsed high-intensity focused ultrasound (pulsed-HIFU) may enhance the fructose-conjugated 4-borono-L-phenylalanine (BPA-Fr) accumulation in tumor lesion using 18F-FBPA-Fr microPET scans.ProceduresTo the mice bearing orthotopic SASC03 human tongue squamous carcinoma xenograft, a 2-min pulsed-HIFU was applied to tumor. Immediately after pulsed-HIFU treatment, 18F-FBPA-Fr was intravenously injected, and biological characterizations including microPET imaging and biodistribution were conducted.ResultsBoth biodistribution studies and microPET imaging performed after intravenous injection of 18F-FBPA-Fr revealed higher tumor uptake in HIFU-treated mice than that of the control. CD31 and Ki-67 histochemical staining of tumor sections and H&E staining of nearby normal tissues revealed no significant difference between the pulsed-HIFU-treated mice and the control.ConclusionThis study demonstrated that pulsed-HIFU was beneficial to the accumulation of boron drug in the head and neck tumor lesion and may enhance the therapeutic efficacy of clinical BNCT.

Monitoring Tumor Response After Histone Deacetylase Inhibitor Treatment Using 3′-Deoxy-3′-[18F]-fluorothymidine PET

PurposeThis study employed 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) microPET scanning to assess the treatment response of histone deacetylase inhibitors (HDACi), e.g., N1-hydroxy-N8-phenyloctanediamide (SAHA) and its iodinated derivative ISAHA, in a hepatoma mouse model.ProceduresThe in vitro cytotoxicity of HDACi in various hepatoma cell lines was determined by MTT assay and flow cytometry. ISAHA and SAHA were used to treat HepG2 hepatoma xenograft-bearing mice. The treatment responses were characterized in terms of tumor burden, microPET imaging, and immunohistochemical staining of tumor sections.ResultsISAHA effectively inhibited HepG2 hepatoma cell survival and tumor growth. A significantly reduced tumor uptake during HDACi treatment was noticed in [18F]FLT microPET imaging, which was consistent with the findings in immunohistochemical staining.ConclusionsISAHA can suppress tumor cell proliferation both in vitro and in vivo. [18F]FLT PET is a promising modality for evaluating the in vivo therapeutic efficacy of HDACi at the early stage of treatment.