Galectin-3 (Gal-3) has been implicated in pancreatic ductal adenocarcinoma (PDAC), and its candidacy as a therapeutic target has been evaluated. Gal-3 is widely upregulated in tumors, and its expression is associated with the development and malignancy of PDAC. In the present study, we demonstrate that a polysaccharide, RN1, purified from the flower of Panax notoginseng binds to Gal-3 and suppresses its expression. In addition, RN1 markedly inhibits PDAC cells growth in vitro, in vivo and in patient-derived xenografts. Mechanistically, RN1 binds to epidermal growth factor receptor (EGFR) and Gal-3, thereby disrupting the interaction between Gal-3 and EGFR and downregulating extracellular-related kinase (ERK) phosphorylation and the transcription factor of Gal-3, Runx1 expression. Inhibiting the expression of Runx1 by RN1, suppresses Gal-3 expression and inactivates Gal-3-associated signaling pathways, including the EGFR/ERK/Runx1, BMP/smad/Id-3 and integrin/FAK/JNK signaling pathways. In addition, RN1 can also bind to bone morphogenetic protein receptors (BMPR1A and BMPR2) and block the interaction between Gal-3 and the BMPRs. Thus, our results suggest that a novel Gal-3 inhibitor RN1 may be a potential candidate for human PDAC treatment via multiple targets and multiple signaling pathways.

The two-photon transition c ð3686Þ ! J=c is studied in a sample of 1:06 Â 10 8 c ð3686Þ decays collected by the BESIII detector. The branching fraction is measured to be ð3:1 AE 0:6ðstatÞ þ0:8 À1:0 ðsystÞÞ Â 10 À4 using J=c ! e þ e À and J=c ! þ À decays, and its upper limit is estimated to be 4:5 Â 10 À4 at the 90% confidence level. This work represents the first measurement of a two-photon transition among charmonium states. The orientation of the c ð3686Þ decay plane and the J=c polarization in this decay are also studied. In addition, the product branching fractions of sequential E1 transitions c ð3686Þ ! cJ and cJ ! J=c ðJ ¼ 0; 1; 2Þ are reported. DOI: 10.1103/PhysRevLett.109.172002 PACS numbers: 14.40.Pq, 13.20.Gd The XYZ [1] particles, which do not fit potential model expectations in QCD theory, have been a key challenge to the QCD description of charmoniumlike states [2]. To fully understand those states, it is necessary to consider the coupling of a charmonium state to a D " D meson pair. These coupled-channel effects, which also play an important role in the charmonium transitions of low-lying states [i.e., from c ð3686Þ to J=c ], are especially relevant for the radiative transition processes [3]. In the well-known electric dipole transitions, the strength of coupled-channel effects will likely be hard to establish, since the accompanying relativistic corrections may be more important [4]. However, the two-photon transition c ð3686Þ ! J=c is more sensitive to the coupled-channel effect and thus provides a unique opportunity to investigate these issues [5].Two-photon spectroscopy has been a very powerful tool for the study of the excitation spectra of a variety of PRL 109, 172002 (2012) P H Y S I C A L R E V I E W L E T T E R S week ending 26 OCTOBER 2012172002-2 systems with a wide range of sizes, such as molecules, atomic hydrogen, and positronium [6]. Studying the analogous process in quarkonium states is a natural extension of this work, in order to gain insight into nonperturbative QCD phenomena. But, so far, two-photon transitions in quarkonia have eluded experimental observation [7][8][9]. For example, in a study of c ð3686Þ ! cJ ðJ ¼ 0; 1; 2Þ reported by the CLEO Collaboration [9], the upper limit for Bðc ð3686Þ ! J=c Þ was estimated to be 1 Â 10 À3 . This Letter presents the first evidence for the two-photon transition c ð3686Þ ! J=c , as well as studies of the orientation of the c ð3686Þ decay plane and the J=c polarization in the decay. The branching fractions of double E1 transitions c ð3686Þ ! ðJ=c Þ cJ through cJ intermediate states are also reported. The upgraded BEPCII [12] at Beijing is a two-ring electron-positron collider. The BESIII detector [10] is an approximately cylindrically symmetric detector which covers 93% of the solid angle around the collision point. In the order of increasing distance from the interaction point, the subdetectors include a 43-layer main wire drift chamber (MDC), a time-of-flight system with two layers in the barrel region and one layer for each end c...