Lidamycin Induces Apoptosis of B-Cell Lymphoma Cells and Inhibits Xenograft Growth in Nude Mice

OBJECTIVE To study the cytotoxicity of Lidamycin (LDM)and its induction of apoptosis in Raji and Daudi cells of B-celllymphoma, and the inhibition of growth of the lymphoma Rajixenograft in nude mice.METHODS MTT assay was used to observe the inhibition byLDM on the proliferation of the Raji and Daudi cells. AnnexinV-FITC/PI double-stain, in combination with flow cytometry(FCM), was used to determine the induction of apoptosis by LDMin Raji cells. The B-cell lymphoma Raji xenograft model in nudemice was set up to detect the in vivo antitumor activity of LDM.RESULTS LDM markedly inhibited the proliferation of theRaji and Daudi cells in vitro, with IC_(50) values of 7.13 × 10^(-11) mol/Land 2.91 × 10^(-10) mol/L, respectively. The apoptotic rates of Rajicells were respectively 77.98% and 67.63% at 0.5 nmol/L and 0.25nmol/L of LDM, indicating an obvious induction of apoptosis inRaji cells. LDM inhibited the formation and growth of humanB-cell lymphoma Raji xenograft in nude mice. The inhibitionrates of tumor growth were respectively 74.9% and 65.2% in LDMat dosage group of 0.05 mg/kg and 0.025 mg/kg, suggesting anapparent prolongation of survival time in the nude mouse bearinglymphoma.CONCLUSION LDM can effectively induce apoptosis of theB-cell lymphoma cells and inhibit the xenograft growth in nudemice.

Advances and challenges in the treatment of esophageal cancer

Esophageal cancer(EC)is one of the most common cancers with high morbidity and mortality rates.EC includes two histological subtypes,namely esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC).ESCC primarily occurs in East Asia,whereas EAC occurs in Western countries.The currently available treatment strategies for EC include surgery,chemotherapy,radiation therapy,molecular targeted therapy,and combinations thereof.However,the prognosis remains poor,and the overall five-year survival rate is very low.Therefore,achieving the goal of effective treatment remains challenging.In this review,we discuss the latest developments in chemotherapy and molecular targeted therapy for EC,and comprehensively analyze the application prospects and existing problems of immunotherapy.Collectively,this review aims to provide a better understanding of the currently available drugs through in-depth analysis,promote the development of new therapeutic agents,and eventually improve the treatment outcomes of patients with EC.

Site-specific PEGylation of lidamycin and its antitumor activity

In this study,N-terminal site-specific mono-PEGylation of the recombinant lidamycin apoprotein(r LDP) of lidamycin(LDM) was prepared using a polyethyleneglycol(PEG) derivative(Mw20 k Da) through a reactive terminal aldehyde group under weak acidic conditions(p H 5.5).The biochemical properties of m PEG-r LDP-AE,an enediyne-integrated conjugate,were analyzed by SDSPAGE,RP-HPLC,SEC-HPLC and MALDI-TOF.Meanwhile,in vitro and in vivo antitumor activity of m PEG-r LDP-AE was evaluated by MTT assays and in xenograft model.The results indicated that m PEGr LDP-AE showed significant antitumor activity both in vitro and in vivo.After PEGylation,m PEG-r LDP still retained the binding capability to the enediyne AE and presented the physicochemical characteristics similar to that of native LDP.It is of interest that the PEGylation did not diminish the antitumor efficacy of LDM,implying the possibility that this derivative may function as a payload to deliver novel tumortargeted drugs.