Role of an autophagy/lysosome pathway in NF-kappa B pathway blocked pancreatic cancer Panc-1 cells
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
Authors: Wu, Ting; Yang, Qi; Chen, Miao; Feng, Yizhong
Abstract
Purpose: To investigate the role of an autophagy/lysosome pathway in NF-kappa B pathway blocked pancreatic cancer Panc-1 cells. Methods: The inhibitory effects of SN50 on pancreatic cancer cell line Panc-1 were detected by MTT assay. After SN50 treatment, autophagy activation was observed by MDC staining and transmission electron microscope (TEM). The expression of light chain 3 (LC3) was detected by immunofluorescence staining. Western blotting analyses were used to detect the expression of apoptosis-related protein p53 and autophagy-related proteins LC3, p62, and Beclin1. Results: Panc-1 cell activity was inhibited after SN50 treatment. The inhibition ratios of Panc-1 cells were (25.76 +/- 5.53)%, (34.35 +/- 4.49)% and (45.22 +/- 1.76)% after treatment of SN50 for 6 h, 12 h, and 24 h, and all changes were significant (P<0.05). Western blotting analysis showed that expressions of apoptotic protein p53, autophagic protein LC3, and Beclin 1 were increased, but the expression of p62 was down-regulated in Panc-1 cells. After SN50 treatment, immunofluorescence showed staining of microtubule-related protein 1 LC3, and MDC fluorescence staining showed increased autophagy bubbles labeled with MDC. Transmission electron microscope (TEM) was used to observe ultrastructure of Panc-1 cells that underwent autophagy after SN50 treatment. Conclusion: The activation of NF-kappa B was blocked by the inhibitor of p65 nuclear translocation, which activated autophagy and induced autophagic cell death in pancreatic cancer Panc-1 cell line.
Clinicopathological characteristics of light chain proximal tubulopathy in Korean patients and the diagnostic usefulness of immunohistochemical staining for immunoglobulin light chain
BMC NEPHROLOGY
Authors: Jung, Minsun; Lee, Youngeun; Lee, Hajeong; Moon, Kyung Chul
Abstract
Background Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea. Methods We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for kappa-LC and lambda-LC was conducted on paraffin-embedded tissues. Results The median age was 63 years, and the male-to-female ratio was 3:2. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal kappa-LC (#1-2) or lambda-LC (#3-5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1-2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3-5. Ig-LC restriction was demonstrated in the proximal tubule as kappa-type in patients #1-2 and as lambda-type in patients #3-5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to kappa- and lambda-LC, although immunofluorescent staining for kappa-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis. Conclusions We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of kappa-type crystals.